bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hellebrin and its aglycone form hellebrigenin display similar in vitro growth inhibitory effects in cancer cells and binding profiles to the alpha subunits of the Na+/K+-ATPase
Authors: Moreno Y Banuls Laetitia , Katz Adriana , Miklos Walter , Cimmino Alessio , Tal Daniel M. , Ainbinder Elena , Zehl Martin , Urban Ernst , Evidente Antonio , Kopp Brigitte , Berger Walter , Feron Olivier , Karlish Steven , Kiss Robert 
Published: April 2013

Abstract

Background
Surface-expressed Na+/K+-ATPase (NaK) has been suggested to function as a non-canonical cardiotonic steroid-binding receptor that activates multiple signaling cascades, especially in cancer cells. By contrast, the current study establishes a clear correlation between the IC50
in vitro growth inhibitory concentration in human cancer cells and the Ki for the inhibition of activity of purified human α1β1 NaK.

Methods
The in vitro growth inhibitory effects of seven cardiac glycosides including five cardenolides (ouabain, digoxin, digitoxin, gitoxin, uzarigenin-rhamnoside, and their respective aglycone forms) and two bufadienolides (gamabufotalin-rhamnoside and hellebrin, and their respective aglycone forms) were determined by means of the MTT colorimetric assay and hellebrigenin-induced cytotoxic effects were visualized by means of quantitative videomicroscopy. The binding affinity of ten of the 14 compounds under study was determined with respect to human α1β1, α2β1 and α3β1 NaK complexes. Lactate releases and oxygen consumption rates were also determined in cancer cells treated with these various cardiac glycosides.

Results
Although cardiotonic steroid aglycones usually display weaker binding affinity and in vitro anticancer activity than the corresponding glycoside, the current study demonstrates that the hellebrin / hellebrigenin pair is at odds with respect to this rule. In addition, while some cardiac steroid glycosides (e.g., digoxin), but not the aglycones, display a higher binding affinity for the α2β1 and α3β1 than for the α1β1 complex, both hellebrin and its aglycone hellebrigenin display ~2-fold higher binding affinity for α1β1 than for the α2β1 and α3β1 complexes. Finally, the current study highlights a common feature for all cardiotonic steroids analyzed here, namely a dramatic reduction in the oxygen consumption rate in cardenolide- and bufadienolide-treated cells, reflecting a direct impact on mitochondrial oxidative phosphorylation.

Conclusions
Altogether, these data show that the binding affinity of the bufadienolides and cardenolides under study is usually higher for the α2β1 and α3β1 than for the α1β1 NaK complex, excepted for hellebrin and its aglycone form, hellebrigenin, with hellebrigenin being as potent as hellebrin in inhibiting in vitro cancer cell growth.
Members of the high mobility group B protein family are dynamically expressed in embryonic neural stem cells
Authors: Abraham Ariel B , Bronstein Robert , Chen Emily I , Koller Antonius , Ronfani Lorenza , Maletic-Savatic Mirjana , Tsirka Stella E 
Published: April 2013

Abstract
Neural Stem Cells (NSCs) are a distinct group of cells present in the embryonic and adult mammalian central nervous system (CNS) that are able to differentiate into neurons, astrocytes and oligodendrocytes. As NSC proliferation declines with age, factors that regulate this process need to be defined. To search for NSC regulatory factors, we performed a quantitative shotgun proteomics study that revealed that members of the High Mobility Group B (HMGB) family are highly expressed in NSCs. Using a neurosphere assay, we report the differential expression of HMGB 1, 2, 3, and 4 mRNAs in proliferating NSCs isolated from various time points during embryonic development, as well as the dynamic expression of HMGB1 and B2 mRNAs and proteins in differentiating embryonic NSCs. Expression of HMGB2 underwent the most dramatic changes during the developmental ages examined; as a result, we assessed its role in NSC proliferation and differentiation. We report the predominance of small diameter HMGB2-/- neurospheres in comparison to wild-type, which correlated with increased proliferation in these smaller HMGB2-/- neurospheres. Our data suggest that HMGB2 plays a regulatory role in NSC cell proliferation and maintenance pathways.
Growth, structure, morphology, and magnetic properties of Ni ferrite films
Authors: Dong Chunhui , Wang Gaoxue , Guo Dangwei , Jiang Changjun , Xue Desheng 
Published: April 2013

Abstract
The morphology, structure, and magnetic properties of nickel ferrite (NiFe2O4) films fabricated by radio frequency magnetron sputtering on Si(111) substrate have been investigated as functions of film thickness. Prepared films that have not undergone post-annealing show the better spinel crystal structure with increasing growth time. Meanwhile, the size of grain also increases, which induces the change of magnetic properties: saturation magnetization increased and coercivity increased at first and then decreased. Note that the sample of 10-nm thickness is the superparamagnetic property. Transmission electron microscopy displays that the film grew with a disorder structure at initial growth, then forms spinel crystal structure as its thickness increases, which is relative to lattice matching between substrate Si and NiFe2O4.
Development of dextran nanoparticles for stabilizing delicate proteins
Authors: Wu Fei , Zhou Zhihua , Su Jing , Wei Liangming , Yuan Weien , Jin Tuo 
Published: April 2013

Abstract
One of the most challenging problems in the development of protein pharmaceuticals is to deal with stabilities of proteins due to its complicated structures. This study aims to develop a novel approach to stabilize and encapsulate proteins into dextran nanoparticles without contacting the interface between the aqueous phase and the organic phase. The bovine serum albumin, granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), β-galactosidase, and myoglobin were selected as model proteins. The proteins were added into an aqueous solution containing the dextran and polyethylene glycol, and then encapsulated into dextran nanoparticles by aqueous-aqueous freezing-induced phase separation. The encapsulation efficiency and recovery of dextran nanoparticles were determined. The dextran nanoparticles loaded with proteins were characterized by scanning electron microscopy and particle size analysis. The protein aggregation was determined by size-exclusion chromatography-high-performance chromatography, and the bioactivity of proteins recovered during formulation steps was determined. The bioactivity of GM-CSF, G-CSF, and β-galactosidase were examined by the proliferation of TF-1 cell, NSF-60 cell, and ortho-nitrophenyl-β-galactoside assay, respectively. The results of bioactivity recovered show that this novel dextran nanoparticle can preserve the protein's bioactivity during the preparation process. LysoSensor™ Yellow/Blue dextran, a pH-sensitive indicator with fluorescence excited at two channels, was encapsulated into dextran nanoparticles to investigate the ability of dextran nanoparticles to resist the acidic microenvironment (pH < 2.5). The result shows that the dextran nanoparticles attenuate the acidic microenvironment in the poly (lactic-co-glycolic acid) microsphere by means of the dilution effect. These novel dextran nanoparticles provided an appealing approach to stabilize the delicate proteins for administration.
Aquareovirus protein VP6 colocalizes with NS80 protein in infected and transfected cells
Authors: Wen Dawei , Yan Liming , Shao Ling , Guo Hong , Li Xiaoming , Fang Qin 
Published: April 2013

Abstract

Background
Aquareovirus particle is comprised of central core and outer capsid, which is built by seven structural proteins (VP1-VP7). The protein VP6 has been identified to be a clamp protein of stabilizing inner core frame VP3, and bridging outer shell protein VP5. However, the biological properties of VP6 in viral life cycle remain unknown.

Results
The recombinant VP6 (rVP6) of aquareovirus was expressed in E. coli, and the polyclonal antibody against VP6 was generated by using purified rVP6 in this study. Following the preparation of VP6 antibody, the VP6 component in aquareovirus infected cells and purified viral particles was detected by Immunoblotting (IB) assay. Furthermore, using Immunofluorescence (IF) microscopy, singly transfected VP6 protein was observed to exhibit a diffuse distribution mainly in the cytoplasm, while it appeared inclusion phenotype in infected cells. Meanwhile, inclusion structures were also identified when VP6 was coexpressed with nonstructural protein NS80 in cotransfected cells.

Conclusions
VP6 can be recruited by NS80 to its inclusions in both infected and transfected cells. The colocalization of VP6 and NS80 is corresponding to their homologous proteins σ2 and μNS in MRV. Our results suggest that VP6 may play a significant role in viral replication and particle assembly.
Effects of continuous renal replacement therapy on renal inflammatory cytokines during extracorporeal membrane oxygenation in a porcine model
Authors: Yimin Hu , Wenkui Yu , Jialiang Shi , Qiyi Chen , Juanhong Shen , Zhiliang Lin , Changsheng He , Ning Li , Jieshou Li 
Published: April 2013

Abstract

Background
Extracorporeal membrane oxygenation (ECMO) has been recommended for the treatment of patients with acute, potentially reversible, life-threatening respiratory failure which unresponsive to conventional therapy. But it is unclear about how ECMO affects renal tissue.

Methods
Twenty-four piglets weighing 25 to 32 kg were used in this experiment. The piglets were randomly allocated to 4 groups of 6 animals each: sham group (S group), control group (C group), VV-ECMO group (E group), VV-ECMO combined with CRRT group (EC group). The piglets were sacrificed and the kidney tissue were harvest to determine the levels of IL-1β, IL-6, TNF-α and NF-КB by using the ELISA and RT-PCR method, respectively.

Results
Compared with C group and S group, E group renal tissue IL-1β, IL-6, TNF-α and NF-КB expression increased significantly, respectively (p < 0.01). Compared with E group, EC group showed renal tissue IL-1β, IL-6, TNF-α and NF-КB expression decreased significantly, respectively (p < 0.05).

Conclusion
ECMO enables to inflammatory cytokines including IL-1β, IL-6, TNFα, NF-КB released significantly, renal function impaired and immune homeostasis were to imbalance; ECMO combined with CRRT treatment can alleviate levels of inflammatory cytokines, maintain immune homeostasis balance and thus ameliorate the ECMO-related acute kidney injury(AKI).
Enhancement of fermentable sugar yields by α-xylosidase supplementation of commercial cellulases
Authors: Jabbour Dina , Borrusch Melissa S , Banerjee Goutami , Walton Jonathan D 
Published: April 2013

Abstract

Background
Although α-linked xylose is a major constituent of the hemicelluloses of land plants, few secreted α-xylosidases have been described from fungi or bacteria. AxlA of Aspergillus niger is a secreted α-xylosidase that was earlier shown to promote the release of free glucose (Glc) and xylose (Xyl) from substrates containing α-linked xylose, including isoprimeverose (IP), the heptasaccharide subunit of pea xyloglucan (XG), and tamarind XG.

Results
The utility of AxlA for enhancing release of free Glc and Xyl in combination with commercial enzyme cocktails from dicotyledonous and monocotyledonous plants was examined. Without AxlA supplementation, a mixture of CTec2 and HTec2 (both of which are derived from T. reesei) did not release significant levels of Glc from pea XG or tamarind XG. This is consistent with their lack of detectable α-xylosidase activity using model substrates. On alkaline hydrogen peroxide-pretreated corn stover, supplementation of CTec2/HTec2 (at a loading of 2.5 mg/g glucan) with AxlA (at a loading of 8 mg/g glucan) increased Glc yields from 82% to 88% of the total available Glc and increased Xyl yields from 55% to 60%. AxlA supplementation also improved Glc yields from corn stover treated with the commercial cellulase Accellerase 1000. The AxlA enhancement was not a general protein effect because bovine serum albumin or bovine gamma-globulin at similar concentrations did not enhance Glc yields from corn stover in response to CTec2/HTec2. Supplementation of CTec2/HTec2 with AxlA did not enhance Glc release from pretreated green or etiolated pea tissue. However, AxlA did enhance Glc and Xyl yields compared to CTec2/HTec2 alone from another dicotyledonous herbaceous plant, Chenopodium album (lamb’s quarters).

Conclusion
Supplementation of commercial cellulase cocktails with AxlA enhances yields of Glc and Xyl from some biomass substrates under some conditions, and may prove useful in industrial lignocellulose conversion.
Paediatric Visceral Leishmaniasis in Italy: a ‘One Health’ approach is needed
Authors: Lorusso Vincenzo , Dantas-Torres Filipe , Caprio Francesco , Manzionna Mariano , Santoro Nicola , Baneth Gad , Otranto Domenico 
Published: April 2013

Abstract
Here we describe a case of paediatric visceral leishmaniasis recorded in an infant initially suspected for acute lymphoblastic leukaemia due to the clinical and haematological presentation. Eventually the patient was found positive for Leishmania infantum infection and successfully treated. This case emphasises how pivotal a ‘One Health’ approach is for diagnosing this zoonotic disease; highlighting the importance of including Visceral Leishmaniasis in the differential diagnosis of leukaemia-like syndromes in infants travelling to, and living in, the Mediterranean region.
Development and characterization of a high-throughput in vitro cord formation model insensitive to VEGF inhibition
Authors: Falcon Beverly L , O’Clair Belinda , McClure Don , Evans Glenn F , Stewart Julie , Swearingen Michelle L , Chen Yuefeng , Allard Kevin , Lee Linda N , Neote Kuldeep , McEwen Dyke P , Uhlik Mark T , Chintharlapalli Sudhakar 
Published: April 2013

AbstractBackgroundAnti-VEGF therapy reduces tumor blood vessels, however, some vessels always remain. These VEGF insensitive vessels may help support continued tumor growth and metastases. Manyin vitroassays examining multiple steps of the angiogenic process have been described, but the majority of these assays are sensitive to VEGF inhibition. There has been little focus on the development of high-throughput,in vitroassays to model the vessels that are insensitive to VEGF inhibition.MethodsHere, we describe a fixed end-point and kinetic, high-throughput stem cell co-culture model of cord formation.ResultsIn this system, cords develop within 24 hours, at which point they begin to lose sensitivity to VEGF inhibitors, bevacizumab, and ramucirumab. Consistent with the hypothesis that other angiogenic factors maintain VEGF-independent vessels, pharmacologic intervention with a broad spectrum anti-angiogenic antagonist (suramin), a vascular disrupting agent (combretastatin), or a combination of VEGF and Notch pathway inhibitors reduced the established networks. In addition, we used ourin vitroapproach to develop anin vivoco-implant vasculogenesis model that connects with the endogenous vasculature to form functional blood vessels. Similar to thein vitrosystem, over time these vessels become insensitive to VEGF inhibition.ConclusionTogether, these models may be used to identify novel drugs targeting tumor vessels that are not sensitive to VEGF inhibition.
Publication bias in animal research: a systematic review protocol
Authors: Briel Matthias , Müller Katharina F , Meerpohl Joerg J , von Elm Erik , Lang Britta , Motschall Edith , Gloy Viktoria , Lamontagne Francois , Schwarzer Guido , Bassler Dirk 
Published: April 2013

Abstract

Background
Systematic reviews and meta-analyses of pre-clinical studies, in vivo animal experiments in particular, can influence clinical care. Publication bias is one of the major threats of validity in systematic reviews and meta-analyses. Previous empirical studies suggested that systematic reviews and meta-analyses have become more prevalent until 2010 and found evidence for compromised methodological rigor with a trend towards improvement. We aim to comprehensively summarize and update the evidence base on systematic reviews and meta-analyses of animal studies, their methodological quality and assessment of publication bias in particular.

Methods/Design
The objectives of this systematic review are as follows:

To investigate the epidemiology of published systematic reviews of animal studies until present.

To examine methodological features of systematic reviews and meta-analyses of animal studies with special attention to the assessment of publication bias.

To investigate the influence of systematic reviews of animal studies on clinical research by examining citations of the systematic reviews by clinical studies.

Eligible studies for this systematic review constitute systematic reviews and meta-analyses that summarize in vivo animal experiments with the purpose of reviewing animal evidence to inform human health. We will exclude genome-wide association studies and animal experiments with the main purpose to learn more about fundamental biology, physical functioning or behavior.
In addition to the inclusion of systematic reviews and meta-analyses identified by other empirical studies, we will systematically search Ovid Medline, Embase, ToxNet, and ScienceDirect from 2009 to January 2013 for further eligible studies without language restrictions.
Two reviewers working independently will assess titles, abstracts, and full texts for eligibility and extract relevant data from included studies. Data reporting will involve a descriptive summary of meta-analyses and systematic reviews.

Discussion
Results are expected to be publicly available later in 2013 and may form the basis for recommendations to improve the quality of systematic reviews and meta-analyses of animal studies and their use with respect to clinical care.
Influence of Zn2+ doping on the structural and surface morphological properties of nanocrystalline Ni-Cu spinel ferrite
Authors: Awati Vidyadhar V , Rathod Sopan M , Mane Maheshkumar L , Mohite Kakasaheb C 
Published: April 2013

Abstract
Ni0.8-x
Cu0.2Zn
x
Fe2O4 (x = 0.0 ≤ 0.6 with steps of 0.2) ferrite nanophase was achieved by sol–gel auto-combustion technique. The as-prepared samples were thermally characterized by thermogravimetry/differential thermal analysis to obtain firing temperature of the materials. The X-ray diffraction pattern indicates the formation of a single-phase cubic spinel structure and shows strong influence of the incorporation of Zn2+ metal ions on the spinel structure. The annealing treatment does not alter the crystal structure but increases the crystallinity of the samples. The morphological investigations and nanometric sizes of the samples were studied by scanning electron microscopy and transmission electron microscopy. The crystallographic texture due to annealing and Zn2+ ion doping was systematically investigated by Fourier transform infrared spectroscopy.
MMP-2 mediates local degradation and remodeling of collagen by annulus fibrosus cells of the intervertebral disc
Authors: Rastogi Anshu , Kim Hyunchul , Twomey Julianne D , Hsieh Adam H 
Published: April 2013

Abstract
Introduction
Degeneration of the intervertebral disc (IVD) is characterized by marked degradation and restructuring of the annulus fibrosus (AF). Although several matrix metalloproteinases (MMPs) have been found to be more prevalent in degenerate discs, their coordination and function within the context of the disease process are still not well understood. In this study, we sought to determine whether MMP-2 is associated with degenerative changes in the AF and to identify the manner by which AF cells use MMP-2.

Methods
Two established animal models of disc degeneration, static compression and transannular needle puncture of rodent caudal discs, were examined for MMP-2 immunopositivity. With lentiviral transduction of an shRNA expression cassette, we screened and identified an effective shRNA sequence for generating stable RNA interference to silence MMP-2 expression in primary rat AF cells. Gelatin films were used to compare gelatinase activity and spatial patterns of degradation between transduced cells, and both noninfected and nonsense shRNA controls. The functional significance of MMP-2 was determined by assessing the ability for cells to remodel collagen gels.

Results
Both static compression and 18-g annular puncture of rodent caudal discs stimulated an increase in MMP-2 activity with concurrent lamellar disorganization in the AF, whereas 22-g and 26-g needle injuries did not. To investigate the functional role of MMP-2, we established lentivirus-mediated RNAi to induce stable knockdown of transcript levels by as much as 88%, and protein levels by as much as 95% over a 10-day period. Culturing transduced cells on gelatin films confirmed that MMP-2 is the primary functional gelatinase in AF cells, and that MMP-2 is used locally in regions immediately around AF cells. In collagen gels, transduced cells demonstrated an inability to remodel collagen matrices.

Conclusions
Our study indicates that increases in MMP-2 observed in human degenerate discs are mirrored in experimentally induced degenerative changes in rodent animal models. AF cells appear to use MMP-2 in a very directed fashion for local matrix degradation and collagen remodeling. This suggests that MMP-2 may have a functionally significant role in the etiology of degenerative disc disease and could be a potential therapeutic target.
Changes in hospital mortality for United States intensive care unit admissions from 1988 to 2012
Authors: Zimmerman Jack E , Kramer Andrew A , Knaus William A 
Published: April 2013

Abstract
Introduction
A decrease in disease-specific mortality over the last twenty years has been reported for patients admitted to United States (US) hospitals, but data for intensive care patients are lacking. The aim of this study was to describe changes in hospital mortality and case-mix using clinical data for patients admitted to multiple US ICUs over the last 24 years.

Methods
We carried out a retrospective time series analysis of hospital mortality using clinical data collected from 1988 to 2012. We also examined the impact of ICU admission diagnosis and other clinical characteristics on mortality over time. The potential impact of hospital discharge destination on mortality was also assessed using data from 2001 to 2012.

Results
For 482,601 ICU admissions there was a 35% relative decrease in mortality from 1988 to 2012 despite an increase in age and severity of illness. This decrease varied greatly by diagnosis. Mortality fell by > 60% for patients with chronic obstructive pulmonary disease, seizures and surgery for aortic dissection and subarachnoid hemorrhage. Mortality fell by 51% to 59% for six diagnoses, 41% to 50% for seven diagnoses, and 10% to 40% for seven diagnoses. The decrease in mortality from 2001 to 2012 was accompanied by an increase in discharge to post-acute care facilities and a decrease in discharge to home.

Conclusions
Hospital mortality for patients admitted to US ICUs has decreased significantly over the past two decades despite an increase in the severity of illness. Decreases in mortality were diagnosis specific and appear attributable to improvements in the quality of care, but changes in discharge destination and other confounders may also be responsible.