bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antimetastatic Effects of Gambogic Acid are Mediated via the Actin Cytoskeleton and NF‐κB Pathways in SK‐HEP1 Cells
Authors: Park Min‐Seok , Kim Nan‐Hee , Kang Chang‐Won , Oh Chul‐Woong , Kim Gun‐Do 
Published: May 2015

ABSTRACT

Preclinical Research

Hepatocellular carcinoma (HCC) is one of the most malignant and frequent cancers with a high metastatic potential. The prevention of HCC metastasis is a critical target for effective therapies in HCC. Gambogic acid (GA), a natural compound obtained from Garcinia hanburyi has reported anticancer activity in cell lines. However, the antimetastatic mechanisms of GA are unclear, particularly with respect to HCC. In this study, the influence of GA on migration and invasion of SK‐HEP1 cells was evaluated. At concentrations above 0.6 μM, GA reduced cell proliferation in SK‐HEP1 cells without affecting proliferation of noncancerous HEK‐293 cells. GA also suppressed migration and invasion of SK‐HEP1 cells. GA downregulated the expression of the integrin β1/rho family GTPase signaling pathway, suppressed the actin rearrangement related to cell cytoskeleton and migration and decreased matrix metalloproteinases MMP‐2, MMP‐9, and NF‐κB expression involved in cancer invasion. These results suggest that GA may be a potential lead in developing an antimetastatic therapeutic for the treatment of HCC. © 2015 Wiley Periodicals, Inc. Drug Dev Res 73 : 132–142, 2015. © 2015 Wiley Periodicals, Inc.
In Vivo Wound‐Healing Effects of Novel Benzalkonium Chloride‐Loaded Hydrocolloid Wound Dressing
Authors: Jin Sung Giu , Yousaf Abid Mehmood , Jang Sun Woo , Son Mi‐Won , Kim Kyung Soo , Kim Dong‐Wuk , Li Dong Xun , Kim Jong Oh , Yong Chul Soon , Choi Han‐Gon 
Published: May 2015

ABSTRACT

Preclinical Research

The purpose of this study was to evaluate the wound‐healing effects of a novel benzalkonium chloride (BC)‐loaded hydrocolloid wound dressing (HCD). A BC‐loaded HCD was prepared with various constituents using a hot melting method, and its mechanical properties and antimicrobial activities were assessed. The in vivo wound healings of the BC‐loaded HCD in various would models were evaluated in rats compared with a commercial wound dressing, Duoderm™. This BC‐loaded HCD gave better skin adhesion, swelling, mechanical strength, and flexibility compared with the commercial wound dressing. It showed excellent antimicrobial activity against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. In addition, as compared with the commercial wound dressing, it showed more improved wound healings and tissue restoration effect on the excision, infection, and abrasion wounds in rats. Thus, this novel BC‐loaded HCD would be an excellent alternative to the commercial wound dressing for treatment of various wounds. Drug Dev Res 73 : 157–165, 2015. © 2015 Wiley Periodicals, Inc.
Healthcare costs and resource utilization of patients with binge‐eating disorder and eating disorder not otherwise specified in the Department of Veterans Affairs
Authors: Bellows Brandon K. , DuVall Scott L. , Kamauu Aaron W.C. , Supina Dylan , Babcock Thomas , LaFleur Joanne 
Published: May 2015

ABSTRACTObjectiveThe objective of this study was to compare the one‐year healthcare costs and utilization of patients with binge‐eating disorder (BED) to patients with eating disorder not otherwise specified without BED (EDNOS‐only) and to matched patients without an eating disorder (NED).MethodsA natural language processing (NLP) algorithm identified adults with BED from clinical notes in the Department of Veterans Affairs (VA) electronic health record database from 2000 to 2011. Patients with EDNOS‐only were identified using ICD‐9 code (307.50) and those with NLP‐identified BED were excluded. First diagnosis date defined the index date for both groups. Patients with NED were randomly matched 4:1, as available, to patients with BED on age, sex, BMI, depression diagnosis, and index month. Patients with cost data (2005–2011) were included. Total healthcare, inpatient, outpatient, and pharmacy costs were examined. Generalized linear models were used to compare total one‐year healthcare costs while adjusting for baseline patient characteristics.ResultsThere were 257 BED, 743 EDNOS‐only, and 823 matched NED patients identified. The mean (SD) total unadjusted one‐year costs, in 2011 US dollars, were $33,716 ($38,928) for BED, $37,052 ($40,719) for EDNOS‐only, and $19,548 ($35,780) for NED patients. When adjusting for patient characteristics, BED patients had one‐year total healthcare costs $5,589 higher than EDNOS‐only (p = 0.06) and $18,152 higher than matched NED patients (p < 0.001).DiscussionThis study is the first to use NLP to identify BED patients and quantify their healthcare costs and utilization. Patients with BED had similar one‐year total healthcare costs to EDNOS‐only patients, but significantly higher costs than patients with NED. © 2015 Wiley Periodicals, Inc. (Int J Eat Disord 2015; 48:1082–1091).
Diversity‐Oriented Synthesis of β‐Lactams and γ‐Lactams by Post‐Ugi Nucleophilic Cyclization: Lewis Acids as Regioselective Switch
Authors: Li Zhenghua , Sharma Upendra Kumar , Liu Zhen , Sharma Nandini , Harvey Jeremy N. , Van der Eycken Erik V. 
Published: May 2015

AbstractHeterocyclic fused α‐methylene β‐lactams were successfully synthesized by a post‐Ugi InIII‐catalyzed intramolecular addition reaction. Switching from InCl3 to AlCl3 led to the regioselective synthesis of α,β‐unsaturated γ‐lactams. Moreover, replacing terminal alkynes by substituted alkynes in the Ugi adducts resulted in the exclusive formation of γ‐lactams with both catalytic systems.
A One‐Pot Copper(II)‐Catalyzed Tandem Synthesis of 2‐Substituted Pyrrolo[1,2‐b]pyridazin‐4(1H)‐ones
Authors: Tan Cun , Xiang Haoyue , He Qian , Yang Chunhao 
Published: May 2015

AbstractA one‐pot copper(II)‐catalyzed tandem synthesis of 2‐substituted pyrrolo[1,2‐b]pyridazin‐4(1H)‐ones from N‐aminopyrroles was developed. This tandem reaction involves a Conrad–Limpach‐type reaction, including the thermal condensation of N‐aminopyrroles with the carbonyl group of β‐oxo esters followed by the cyclization of Schiff base intermediates. Compared to the traditional Conrad–Limpach quinoline synthesis, we herein successfully applied copper(II) as a catalyst in this transformation to furnish 2‐substituted pyrrolo[1,2‐b]pyridazin‐4(1H)‐ones for the first time. Most of the substrates bearing electron‐donating (EDG) and electron‐withdrawing (EWG) groups worked well with this procedure. The corresponding products could be converted directly into diverse pyrrolo[1,2‐b]pyridazine for drug discovery and materials science.
A Coupled Reservoir/Wellbore Model to Simulate the Steam Injection Performance of Horizontal Wells
Authors: Li Mingzhong , Chen Huijuan , Zhang Yanyu , Li Weiwei , Wang Yiping , Yu Meng 
Published: May 2015

AbstractA coupled reservoir/wellbore model of horizontal wells in a steam injection process is presented, which considers the three‐dimensional simultaneous flow of three phases in the reservoir and gas–liquid two‐phase flow in the wellbore. Based on the model, the steam injection performance of a horizontal well is simulated. The pressure, temperature, and steam quality distribution in the wellbore as well as the steam injection profile and reservoir temperature along the horizontal wellbore are discussed. Results show that the wellbore pressure, temperature, and steam quality decrease from the horizontal wellbore heel to the toe. The steam flux rate and reservoir temperature are higher at the wellbore heel and toe. Furthermore, the variations of the steam flux rate and reservoir temperature along the wellbore increase with sustained injections, which is a disadvantage for thermal horizontal wells. Therefore, developing techniques to guarantee a uniform flow along horizontal wellbores is crucial.
Cytochrome P450–mediated warfarin metabolic ability is not a critical determinant of warfarin sensitivity in avian species: In vitro assays in several birds and in vivo assays in chicken
Authors: Watanabe Kensuke P. , Kawata Minami , Ikenaka Yoshinori , Nakayama Shouta M. M. , Ishii Chihiro , Darwish Wageh Sobhi , Saengtienchai Aksorn , Mizukawa Hazuki , Ishizuka Mayumi 
Published: May 2015

Abstract

Coumarin-derivative anticoagulant rodenticides used for rodent control are posing a serious risk to wild bird populations. For warfarin, a classic coumarin derivative, chickens have a high median lethal dose (LD50), whereas mammalian species generally have much lower LD50. Large interspecies differences in sensitivity to warfarin are to be expected. The authors previously reported substantial differences in warfarin metabolism among avian species; however, the actual in vivo pharmacokinetics have yet to be elucidated, even in the chicken. In the present study, the authors sought to provide an in-depth characterization of warfarin metabolism in birds using in vivo and in vitro approaches. A kinetic analysis of warfarin metabolism was performed using liver microsomes of 4 avian species, and the metabolic abilities of the chicken and crow were much higher in comparison with those of the mallard and ostrich. Analysis of in vivo metabolites from chickens showed that excretions predominantly consisted of 4′-hydroxywarfarin, which was consistent with the in vitro results. Pharmacokinetic analysis suggested that chickens have an unexpectedly long half-life despite showing high metabolic ability in vitro. The results suggest that the half-life of warfarin in other bird species could be longer than that in the chicken and that warfarin metabolism may not be a critical determinant of species differences with respect to warfarin sensitivity. Environ Toxicol Chem 2015;34:2328–2334. © 2015 SETAC
Tree ring analysis of hydro‐climatic thresholds that trigger ice jams on the Mistassini River, Quebec
Authors: Lagadec Annie , Boucher Étienne , Germain Daniel 
Published: May 2015

AbstractThis study documents the spatiotemporal variations in the frequency and magnitude of ice jams in the Mistassini River and applies that information to the identification of the hydro‐climatic threshold conditions associated with major events. Ice jams cause severe upheavals in water flow, which result in flooding upstream of the ice jam front, and therefore represent a significant geohazard to riparian populations. To analyze the spatiotemporal variations in the magnitude–frequency of ice jams, the Mistassini River was first divided into six different sites representing different geomorphological contexts. A 50‐year ice jam chronology was constructed from 85 damaged trees from all of the study sites. This chronology was then coupled with hydro‐climatic variables to construct classification trees, which helped identify the conditions and hydro‐climatic thresholds favourable to the triggering of ice jams in a predictive model. The results indicate complex interactions between the characteristics of flow, ice cover and river morphology that affect the frequency and magnitude of ice jam events on the Mistassini River. These factors affect the frequency and magnitude of ice jam events. The triggering of extreme events seems particularly influenced by exceptional ice conditions and sites with high sinuosity and islands. Copyright © 2015 John Wiley & Sons, Ltd.
In vivobiological response to highly cross‐linked and vitamin e‐doped polyethylene—a particle‐Induced osteolysis animal study
Authors: Huang Chang‐Hung , Lu Yung‐Chang , Chang Ting‐Kuo , Hsiao I‐Lin , Su Yi‐Ching , Yeh Shu‐Ting , Fang Hsu‐Wei , Huang Chun‐Hsiung 
Published: May 2015

AbstractPolyethylene particle‐induced osteolysis is the primary limitation in the long‐term success of total joint replacement with conventional ultra high molecular weight polyethylene (UHMWPE). Highly cross‐linked polyethylene (HXLPE) and vitamin E‐doped cross‐linked polyethylene (VE‐HXLPE) have been developed to increase the wear resistance of joint surfaces. However, very few studies have reported on the incidence of particle‐induced osteolysis for these novel materials. The aim of this study was to use a particle‐induced osteolysis animal model to compare thein vivobiological response to different polymer particles. Three commercially available polymers (UHMWPE, HXLPE, and VE‐HXLPE) were compared. Osseous properties including the bone volume relative to the tissue volume (BV/TV), trabecular thickness (Tb. Th), and bone mineral density (BMD) were examined using micro computed tomography. Histological analysis was used to observe tissue inflammation in each group. This study demonstrated that the osseous properties and noticeable inflammatory reactions were obviously decreased in the HXLPE group. When compared with the sham group, a decrease of 12.7% was found in BV/TV, 9.6% in BMD and 8.3% in Tb.Th for the HXLPE group. The heightened inflammatory response in the HXLPE group could be due to its smaller size and greater amount of implanted particles. Vitamin E diffusedin vivomay not affect the inflammatory and osteolytic responses in this model. The morphological size and total cumulative amount of implanted particles could be critical factors in determining the biological response. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 561–567, 2016.
Dimensionally stable and bioactive membrane for guided bone regeneration: An in vitro study
Authors: Rowe Matthew J. , Kamocki Krzysztof , Pankajakshan Divya , Li Ding , Bruzzaniti Angela , Thomas Vinoy , Blanchard Steve B. , Bottino Marco C. 
Published: May 2015

AbstractComposite fibrous electrospun membranes based on poly(dl‐lactide) (PLA) and poly(ε‐caprolactone) (PCL) were engineered to include borate bioactive glass (BBG) for the potential purposes of guided bone regeneration (GBR). The fibers were characterized using scanning and transmission electron microscopies, which respectively confirmed the submicron fibrous arrangement of the membranes and the successful incorporation of BBG particles. Selected mechanical properties of the membranes were evaluated using the suture pullout test. The addition of BBG at 10 wt % led to similar stiffness, but more importantly, it led to a significantly stronger (2.37 ± 0.51 N mm) membrane when compared with the commercially available Epiguide® (1.06 ± 0.24 N mm) under hydrated conditions. Stability (shrinkage) was determined after incubation in a phosphate buffer solution from 24 h up to 9 days. The dimensional stability of the PLA:PCL‐based membranes with or without BBG incorporation (10.07–16.08%) was similar to that of Epiguide (14.28%). Cell proliferation assays demonstrated a higher rate of preosteoblasts proliferation on BBG‐containing membranes (6.4‐fold) over BBG‐free membranes (4‐ to 5.8‐fold) and EpiGuide (4.5‐fold), following 7 days of in vitro culture. Collectively, our results demonstrated the ability to synthesize, via electrospinning, stable, polymer‐based submicron fibrous BBG‐containing membranes capable of sustaining osteoblastic attachment and proliferation—a promising attribute in GBR. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 594–605, 2016.
The influence of poly(ethylene glycol) ether tetrasuccinimidyl glutarate on the structural, physical, and biological properties of collagen fibers
Authors: Sanami Mohammad , Sweeney India , Shtein Zvi , Meirovich Sigal , Sorushanova Anna , Mullen Anne Maria , Miraftab Mohsen , Shoseyov Oded , O'Dowd Colm , Pandit Abhay , Zeugolis Dimitrios I. 
Published: May 2015

AbstractVarious chemical, natural, or synthetic in origin, crosslinking methods have been proposed over the years to stabilise collagen fibers. However, an optimal method has yet to be identified. Herein, we ventured to assess the potential of 4‐star poly(ethylene glycol) ether tetrasuccinimidyl glutarate, as opposed to glutaraldehyde (GTA), genipin and carbodiimide, on the structural, physical and biological properties of collagen fibers. The 4‐star poly(ethylene glycol) ether tetrasuccinimidyl glutarate induced an intermedium surface smoothness, denaturation temperature and swelling. The 4‐star poly(ethylene glycol) ether tetrasuccinimidyl glutarate fibers had significantly higher stress at break values than the carbodiimide fibers, but significantly lower than the GTA and genipin fibers. With respect to strain at break, no significant difference was observed among the crosslinking treatments. The 4‐star poly(ethylene glycol) ether tetrasuccinimidyl glutarate fibers exhibited significantly higher cell metabolic activity and DNA concentration that all other crosslinking treatments, promoted consistently cellular elongation along the longitudinal fiber axis and by day 7 they were completely covered by cells. Collectively, this work clearly demonstrates the potential of 4‐star poly(ethylene glycol) ether tetrasuccinimidyl glutarate as collagen crosslinker. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 914–922, 2016.
Serum 25-Hydroxyvitamin D Levels: Variability, Knowledge Gaps, and the Concept of a Desirable Range
Authors: El-Hajj Fuleihan Ghada , Bouillon Roger , Clarke Bart , Chakhtoura Marlene , Cooper Cyrus , McClung Michael , Singh Ravinder J 
Published: May 2015

ABSTRACT

Hypovitaminosis D is prevalent worldwide but proportions vary widely between regions, depending on genetic and lifestyle factors, the threshold to define deficiency, and accuracy of 25-hydroxyvitamin D (25OHD) assays used. Latitude, pollution, concealing clothing, sun exposure, gender, dietary habits, and lack of government regulation account for up to 50% in variations in serum 25OHD levels, whereas genetic polymorphisms in the vitamin D pathway account for less than 5%. Organizations/societies have developed guidelines for recommended desirable 25OHD levels and vitamin D doses to reach them, but their applicability across age groups and populations are still debated. This article and the accompanying online Supporting Information highlight sources of variations in circulating 25OHD levels, uncertainties and knowledge gaps, and analytical problems facing 25OHD assays, while keeping efficacy and safety data as the dominant factors when defining a desirable range for 25OHD levels. We propose a desirable range of 20 to 40 ng/mL (50 to 100 nmol/L), provided precise and accurate assays are used. Although slightly lower levels, 15 to 20 ng/mL, may be sufficient for some infants and adults, higher levels, 40 to 60 ng/mL, may still be safe. This desirable range allows physicians to tailor treatment while taking season, lifestyle, vitamin D intake, and other sources of variation into account. We reserve 25OHD measurements for at-risk patients, defined by disease or lifestyle, and the use of 25OHD assays calibrated against the recommended international standards. Most target groups reach desirable target levels by a daily intake of 400 to 600 IU for children and 800 IU for adults. A total daily allowance of vitamin D of up to 1000 IU in the pediatric age groups, and up to 2000 IU in adults, tailored to an individual patient risk profile, is probably safe over long durations. Additional data are needed to validate the proposed range and vitamin D doses, especially in children, pregnant women, and non-white populations. © 2015 American Society for Bone and Mineral Research.
Global Gene Deregulations in FASN Silenced Retinoblastoma Cancer Cells: Molecular and Clinico‐Pathological Correlations
Authors: Sangeetha Manoharan , Deepa Perinkulam Ravi , Rishi Pukhraj , Khetan Vikas , Krishnakumar Subramanian 
Published: May 2015

AbstractActivation of fatty acid synthase (FASN) enzyme in the de novo lipogenic pathway has been reported in various cancers including retinoblastoma (RB), a pediatric ocular cancer. The present study investigates lipogenesis‐dependent survival of RB cancer cells and the associated molecular pathways in FASN silenced RB cells. The siRNA‐mediated FASN gene knockdown in RB cancer cells (Y79, WERI RB1) repressed FASN mRNA and protein expressions, and decreased cancer cell viability. Global gene expression microarray analysis was performed in optimized FASN siRNA transfected and untransfected RB cells. Deregulation of various downstream cell signaling pathways such as EGFR (n = 55 genes), TGF‐beta (n = 45 genes), cell cycle (n = 41 genes), MAPK (n = 39 genes), lipid metabolism (n = 23 genes), apoptosis (n = 21 genes), GPCR signaling (n = 21 genes), and oxidative phosporylation (n = 18 genes) were observed. The qRT‐PCR validation in FASN knockdown RB cells revealed up‐regulation of ANXA1, DAPK2, and down‐regulation of SKP2, SREBP1c, RXRA, ACACB, FASN, HMGCR, USP2a genes that favored the anti‐cancer effect of lipogenic inhibition in RB. The expression of these genes in primary RB tumor tissues were correlated with FASN expression, based on their clinico‐pathological features. The differential phosphorylation status of the various PI3K/AKT pathway proteins (by western analysis) indicated that the FASN gene silencing indeed mediated apoptosis in RB cells through the PI3K/AKT pathway. Scratch assay clearly revealed that FASN silencing reduced the invading property of RB cancer cells. Dependence of RB cancer cells on lipid metabolism for survival and progression is implicated. Thus targeting FASN is a promising strategy in RB therapy. J. Cell. Biochem. 116: 2676–2694, 2015. © 2015 Wiley Periodicals, Inc.
C/EBPβ Mediates TNF‐α‐Induced Cancer Cell Migration by Inducing MMP Expression Dependent on p38 MAPK
Authors: Xia Peiyi , Zhang Rui , Ge Gaoxiang 
Published: May 2015

ABSTRACTTumor necrosis factor (TNF)‐α is a pleiotropic cytokine that triggers cell proliferation, cell death, or inflammation. Besides its cytotoxic effect on cancer cells, TNF‐α exerts tumor promoting activity. Aberrant TNF‐α signaling promotes cancer cell motility, invasiveness, and enhances cancer metastasis. Exaggerated tumor cell migration, invasion, and metastasis by TNF‐α has been attributed to the activation of NF‐κB signaling. It is yet to be elucidated if other signaling pathways and effector molecules are involved in TNF‐α‐induced cancer cell migration and metastasis. Expression of C/EBPβ, a transcription factor involved in metabolism, inflammation, and cancer, is increased upon TNF‐α treatment. TNF‐α induces C/EBPβ expression by enhancing its transcription and protein stability. Activation of p38 MAPK, but not NF‐κB or JNK, is responsible for TNF‐α‐induced stabilization of C/EBPβ protein. C/EBPβ is involved in TNF‐α‐induced cancer cell migration. Knockdown of C/EBPβ inhibits TNF‐α‐induced cell migration, while overexpression of C/EBPβ increases migration of cancer cells. C/EBPβ is translated into transcriptional activator LAP1 and LAP2 and transcriptional repressor LIP utilizing alternative in‐frame translation start sites. Despite TNF‐α induces expression of all three isoforms, LAP1/2, but not LIP, promote cancer cell migration. TNF‐α induced MMP1/3 expression, which was abrogated by C/EBPβ knockdown or p38 MAPK inhibition. MMP inhibitor or knockdown of MMP1/3 diminished TNF‐α‐ and C/EBPβ‐induced cell migration. Thus, C/EBPβ mediates TNF‐α‐induced cancer cell migration by inducing MMP1/3 expression, and may participate in the regulation of inflammation‐associated cancer metastasis. J. Cell. Biochem. 116: 2766–2777, 2015. © 2015 Wiley Periodicals, Inc.