bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oxidative Stress Induced by Curcumin Promotes the Death of Cutaneous T-cell Lymphoma (HuT-78) by Disrupting the Function of Several Molecular Targets
Authors: Khan Mohammad Aslam , Gahlot Satindra , Majumdar Sekhar 
Published: June 2012

Abstract
Curcumin is known to exert its anticancer effect either by scavenging or by generating reactive oxygen species (ROS). In this study, we report that curcumin-mediated rapid generation of ROS induces apoptosis by modulating different cell survival and cell death pathways in HuT-78 cells. Curcumin induces the activation of caspase-8, -2, and -9, alteration of mitochondrial membrane potential, release of cytochrome c, and activation of caspase-3 and concomitant PARP cleavage, but the addition of caspase inhibitors only partially blocked the curcumin-mediated apoptosis. Curcumin also downregulates the expression of antiapoptotic proteins c-FLIP, Bcl-xL, cellular inhibitor of apoptosis protein, and X-linked IAP in a ROS-dependent manner. Curcumin disrupts the integrity of IKK and beclin-1 by degrading Hsp90. Degradation of IKK leads to the inhibition of constitutive NF-κB. Degradation of beclin-1 by curcumin leads to the accumulation of autophagy-specific marker, microtubule-associated protein-I light chain 3 (LC3), LC3-I. Our findings indicate that HuT-78 cells are vulnerable to oxidative stress induced by curcumin and as a result eventually undergo cell death. Mol Cancer Ther; 11(9); 1873–83. ©2012 AACR.
Endothelial Cells Require Related Transcription Enhancer Factor-1 for Cell–Cell Connections Through the Induction of Gap Junction Proteins
Authors: An Xiaojin , Jin Yi , Philbrick Melissa J. , Wu Jiaping , Messmer-Blust Angela , Song Xiaoxiao , Cully Brittany L. , He Ping , Xu Ming , Duffy Heather S. , Li Jian 
Published: June 2012

Objective—
Capillary network formation represents a specialized endothelial cell function and is a prerequisite to establish a continuous vessel lumen. Formation of endothelial cell connections that form the vascular structure is regulated, at least in part, at the transcriptional level. We report here that related transcription enhancer factor-1 (RTEF-1) plays an important role in vascular structure formation.

Methods and Results—
Knockdown of RTEF-1 by small interfering RNA or blockage of RTEF-1 function by the transcription enhancer activators domain decreased endothelial connections in a Matrigel assay, whereas overexpression of RTEF-1 in endothelial cells resulted in a significant increase in cell connections and aggregation. In a model of oxygen-induced retinopathy, endothelial-specific RTEF-1 overexpressing mice had enhanced angiogenic sprouting and vascular structure remodeling, resulting in the formation of a denser and more highly interconnected superficial capillary plexus. Mechanistic studies revealed that RTEF-1 induced the expression of functional gap junction proteins including connexin 43, connexin 40, and connexin 37. Blocking connexin 43 function inhibited RTEF-1–induced endothelial cell connections and aggregation.

Conclusion—
These findings provide novel insights into the transcriptional control of endothelial function in the coordination of cell–cell connections.
Mast Cells Induce Vascular Smooth Muscle Cell Apoptosis via a Toll-Like Receptor 4 Activation Pathway
Authors: den Dekker Wijnand K. , Tempel Dennie , Bot Ilze , Biessen Erik A. , Joosten Leo A. , Netea Mihai G. , van der Meer Jos W. M. , Cheng Caroline , Duckers Henricus J. 
Published: June 2012

Objective—
Activated mast cells (MCs) release chymase, which can induce vascular smooth muscle cell (VSMC) apoptosis leading to plaque destabilization. Because the mechanism through which MCs release chymase in atherosclerosis is unknown, we studied whether MC-associated VSMC apoptosis is regulated by toll-like receptor 4 (TLR4) signaling.

Methods and Results—

Local recruitment and activation of MCs reduced VSMC content specifically in the cap region of vulnerable plaques in apolipoprotein E knockout mice. Cotreatment with the TLR4 antagonist
Bartonella quintana
lipopolysaccharide prevented this VSMC loss, suggesting an important role for TLR4 signaling in MC-induced VSMC apoptosis. Coculture of VSMCs with MCs activated by the TLR4 agonist
Escherichia coli
lipopolysaccharide increased VSMC apoptosis. Apoptosis was inhibited by TLR4 and chymase blockers, indicating that TLR4 signaling is involved in chymase release in MCs. This pathway was mediated via interleukin-6 because interleukin-6 promoted MC-associated VSMC apoptosis, which was inhibited by blocking chymase release. In addition, TLR4 activation in MCs induced interleukin-6 production, which was reduced by preincubation with either
B. quintana
lipopolysaccharide or an anti-TLR4 antibody.

Conclusion—
We show that MCs promote VSMC apoptosis in vivo. In addition, TLR4 signaling is important in chymase release in MCs and, therefore, in plaque destabilization by regulating VSMC apoptosis.
Extrahepatic High-Density Lipoprotein Receptor SR-BI and ApoA-I Protect Against Deep Vein Thrombosis in Mice
Authors: Brill Alexander , Yesilaltay Ayce , De Meyer Simon F. , Kisucka Janka , Fuchs Tobias A. , Kocher Olivier , Krieger Monty , Wagner Denisa D. 
Published: June 2012

Objective—
Deep vein thrombosis (DVT) and pulmonary embolism are frequent causes of morbidity and mortality. The goal of our study was to determine whether plasma high-density lipoprotein (HDL), which inversely correlates with the risk of cardiovascular events, affects DVT.

Methods and Results—

Using a murine DVT model of inferior vena cava stenosis, we demonstrated that deficiency of the HDL receptor, scavenger receptor class B type I (SR-BI), promotes venous thrombosis. As SR-BI
−/−
mice have increased plasma cholesterol levels and abnormal HDL particles, we tested SR-BI
−/−
mice with an SR-BI liver transgene that normalizes both parameters. These mice also exhibited increased susceptibility to DVT, indicating a protective role of extrahepatic SR-BI. Mice lacking the major HDL apolipoprotein apoA-I or endothelial nitric oxide synthase (eNOS) (a downstream target of endothelial SR-BI signaling) also had a prothrombotic phenotype. Intravenous infusion of human apoA-I, an HDL component and SR-BI ligend, prevented DVT in wild-type but not SR-BI
−/−
or eNOS
−/−
mice, suggesting that its effect is mediated by SR-BI and eNOS. Intravenous apoA-I infusion abolished histamine-induced platelet–endothelial interactions, which are important for DVT initiation.

Conclusion—
An apoA-I (HDL)–SR-BI–eNOS axis is highly protective in DVT and may provide new targets for prophylaxis and treatment of venous thrombosis.
C1q/Tumor Necrosis Factor-Related Protein-3, a Newly Identified Adipokine, Is a Novel Antiapoptotic, Proangiogenic, and Cardioprotective Molecule in the Ischemic Mouse Heart
Authors: Yi Wei , Sun Yang , Yuan Yuexing , Lau Wayne Bond , Zheng Qijun , Wang Xiaoliang , Wang Yajing , Shang Xiying , Gao Erhe , Koch Walter J. , Ma Xin-Liang 
Published: June 2012

Background—
Obesity and diabetes mellitus adversely affect postischemic heart remodeling via incompletely understood mechanisms. C1q/tumor necrosis factor–related protein-3 (CTRP3) is a newly identified adipokine exerting beneficial metabolic regulation, similar to adiponectin. The aim of the present study was to determine whether CTRP3 may regulate postischemic cardiac remodeling and cardiac dysfunction, and, if so, to elucidate the underlying mechanisms.

Methods and Results—

Male adult mice were subjected to myocardial infarction (MI) via left anterior descending coronary artery occlusion. Both the effect of MI on endogenous CTRP3 expression/production and the effect of exogenous CTRP3 (adenovirus or recombinant CTRP3) replenishment on MI injury were investigated. MI significantly inhibited adipocyte CTRP3 expression and reduced the plasma CTRP3 level, reaching a nadir 3 days after MI. CTRP3 replenishment improved survival rate (
P
<0.05), restored cardiac function, attenuated cardiomyocyte apoptosis, increased revascularization, and dramatically reduced interstitial fibrosis (all
P
<0.01). CTRP3 replenishment had no significant effect on cardiac AMP-activated protein kinase phosphorylation but significantly increased Akt phosphorylation and expression of hypoxia inducing factor-1α and vascular endothelial growth factor. Surprisingly, treatment of human umbilical vascular endothelial cells with CTRP3 did not directly affect nitric oxide production or tube formation. However, preconditioned medium from CTRP3-treated cardiomyocytes significantly enhanced human umbilical vascular endothelial cell tube formation, an effect blocked by either pretreatment of cardiomyocytes with a PI3K inhibitor or pretreatment of human umbilical vascular endothelial cells with a vascular endothelial growth factor inhibitor. Finally, the protective effect of adipocyte-conditioned medium against hypoxia-induced cardiomyocyte injury is significantly blunted when CTRP3 is knocked down.

Conclusion—
CTRP3 is a novel antiapoptotic, proangiogenic, and cardioprotective adipokine, the expression of which is significantly inhibited after MI.
Kindergarten teachers’ and their assistants’ knowledge of first aid in Slovenian kindergartens
Authors: Slabe Damjan , Fink Rok 
Published: June 2012

Objective: Rapid physical and mental development in childhood also brings about a high risk of being injured. Since children spend a large amount of their time in kindergarten, there is a possibility that they would be injured while there. Design: A questionnaire for professionals was sent to a Slovenian kindergarten. Setting: The aim of this study is to analyze kindergarten teachers’ theoretical knowledge of first aid in Slovenian kindergartens. Methods: In a randomly selected sample ( N = 487), kindergarten teachers and assistants were included and polled about first aid topics. Results: The results show that teachers and assistants are familiar with the responsibilities related to first aid. In the case of burns, braises and fractures, they would act correctly, but in case of life threatening situations, for example cardiopulmonary resuscitation, intoxication, unconsciousness and asphyxia, less than 20% would properly provide first aid. No statistically significant differences were found between kindergarten teachers’ and assistants’ knowledge ( p > 0.05), but statistically significant differences in age and work experience ( p < 0.05) were found. Kindergarten teachers are aware of their responsibility for children’s lives and are well familiar with non-life threatening situations. In case of an emergency, most respondents would act incorrectly. The results also show that kindergarten teachers and their assistants overestimate their knowledge of first aid. Conclusion: Teaching in kindergarten requires a high level of first aid knowledge both because teachers are often faced with emergency situations and because teachers or assistants are the first to respond in most situations in which an injured child needs help.
Developing gifted children in Hungarian preschool education
Authors: Nagy Iren , Papp Irene 
Published: June 2012

At a conference, a secondary school teacher was very surprised when she heard about the idea of talent development in preschool education. ‘What does it mean?’ she asked. In this paper we answer the above question with a model created by joint research. We describe our method of developing gifted children with the involvement of preschool teachers in an ordinary kindergarten.
Screening of microbial contamination and antimicrobial activity of sea cucumber Holothuria polii
Authors: Omran Nahla EE , Allam Nanis G 
Published: June 2012

Microbiological studies were carried out on microbial contamination and antimicrobial activity of sea cucumber Holothuria polii collected from Mediterranean Sea at Abu-kir shore of Alexandria, Egypt. The obtained results revealed the presence of isolates of five human Gram-negative pathogenic bacteria, representing five genera were identified to species level, including, Esherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella sp. and Shigella sp. In addition, an yeast Candida albicans was isolated. The pathogenic bacteria were identified using API 20E strip system (BioMereux). All collected H. polii specimens were healthy with no external signs of infection. Histopathological study of the tegument, intestine and gonads showed no abnormal changes. The antimicrobial activity of two tegumental ethanol extracts (A and B, differ in the method of dehydration) were tested against wide range of pathogenic bacteria and fungi, including intestinal, skin and nosocomial pathogens and one plant fungal pathogen. The results revealed a remarkable antifungal activity of the extract B at 2.5 mg/ml MIC90, especially on Aspergillus niger, Scloretium sp, C. albicans, Aspergillus flavus and Malassezia furfur, and limited antibacterial activity against Gram-negative bacteria ( Salmonella choleraesuis ATCC 14028 and Aeromonas hydrophila). The domain of bacterial and limited fungal contamination confirms the results that showed strong antifungal activity of investigated extract.
Effects of BQ-788 on amitriptyline-induced cardiovascular toxicity
Authors: Arıcı MAA , Buyukdeligoz M , Kalkan S , Tuncok Y 
Published: June 2012

Objective: We investigated both the effects of the endothelin type B (ETB) receptor antagonist, BQ-788, on amitriptyline-induced cardiotoxicity and the role of ETB receptors on amitriptyline-induced cardiovascular depression. Methods: Male Wistar rats were anaesthetized with urethane/chloralose. Mean arterial pressure (MAP), heart rate (HR) and QRS duration were recorded. Toxicity was induced by amitriptyline infusion (0.94 mg/kg per min) until the 50% inhibition of MAP. In the first protocol, 5% dextrose or BQ-788 bolus was administered to control or experimental group animals, respectively. In the second protocol, after incubation with BQ-788 or 5% dextrose, amitriptyline was infused. Results: Amitriptyline caused a significant decrease in MAP, prolonged QRS duration and decreased HR for both the groups. BQ-788 administration improved MAP (5, 10 and 15 min), shortened the prolonged QRS (5 and 10 minutes) and increased HR (5, 10 and 15 min) compared with dextrose group. While all the amitriptyline-infused rats survived in BQ-788 group, all the amitriptyline-infused rats died within 20 min in dextrose group. In the second protocol, BQ-788 incubation did not cause any statistically significant change in amitriptyline-induced cardiovascular depression. Conclusion: BQ-788 may have beneficial effects in amitriptyline-induced cardiovascular changes via a physiologic antagonism. ETB receptor antagonists may be the promising antidotes for the cardiovascular toxicity with hypotension and bradycardia.
Electroconvulsive therapy training: can it be a model of an entrustable professional activity in a competency program?
Authors: Port Neil , Weiss Alan , Maudsley Ian 
Published: June 2012

Objectives: This paper gives an overview of the teaching and assessment process in electroconvulsive therapy (ECT) provided in the Hunter Region to see if it can be used as a successful example of competency assessment and training. We describe the process and practice of training and credentialing in ECT in the Hunter Region, and compare these with the requirements of an Entrustable Professional Activity (EPA) in particular and competency based training and assessment in general. Conclusion: The intensely supervised ‘hands on’ training and assessment in this program, and the entrusting of successful graduates to perform ECT and related activities with sufficient independence, demonstrate an ‘Entrustable Professional Activity’ as proposed for introduction in the Royal Australian and New Zealand College of Psychiatrists Competency Based Fellowship Program.
Immunomodulatory therapies delay disease progression in multiple sclerosis
Authors: Bergamaschi Roberto , Quaglini Silvana , Tavazzi Eleonora , Amato Maria Pia , Paolicelli Damiano , Zipoli Valentina , Romani Alfredo , Tortorella Carla , Portaccio Emilio , D’Onghia Mariangela , Garberi Francesca , Bargiggia Valeria , Trojano Maria 
Published: June 2012

Background: Few studies have analysed long-term effects of immunomodulatory disease modifying drugs (DMDs). Objective: Assessment of the efficacy of DMDs on long-term evolution of multiple sclerosis, using a Bayesian approach to overcome methodological problems related to open-label studies. Methods: MS patients from three different Italian multiple sclerosis centres were divided into subgroups according to the presence of treatment in their disease history before the endpoint, which was represented by secondary progression. Patients were stratified on the basis of the risk score BREMS (Bayesian risk estimate for multiple sclerosis), which is able to predict the unfavourable long-term evolution of MS at an early stage. Results: We analysed data from 1178 patients with a relapsing form of multiple sclerosis at onset and at least 10 years of disease duration, treated (59%) or untreated with DMDs. The risk of secondary progression was significantly lower in patients treated with DMDs, regardless of the initial prognosis predicted by BREMS. Conclusions: DMDs significantly reduce the risk of multiple sclerosis progression both in patients with initial high-risk and patients with initial low-risk. These findings reinforce the role of DMDs in modifying the natural course of the disease, suggesting that they have a positive effect not only on the inflammatory but also on the neurodegenerative process. The study also confirms the capability of the BREMS score to predict MS evolution.
Long term benefit of multiple sclerosis treatment: an investigation using a novel data collection technique
Authors: Conway Devon S , Miller Deborah M , O’Brien Ralph G , Cohen Jeffrey A 
Published: June 2012

Background: The Knowledge Program (KP) is an initiative to collect self-reported patient data and objective clinician assessments electronically at each outpatient clinical encounter. Available outcomes include the EuroQoL-5D (EQ5D), Patient Health Questionnaire-9 (PHQ9), Multiple Sclerosis Performance Scales (MSPS), and the timed 25-foot walk (T25FW). Objective: This study was designed to use the KP to investigate the long-term benefits of early treatment (ET) in multiple sclerosis (MS). Methods: The KP was queried for patients with relapsing–remitting MS or secondary progressive MS who were ≥5 years from symptom onset. ET was defined as treatment with an approved agent for ≥3 of the first five years after symptom onset. Propensity scores for ET were calculated based on early clinical characteristics. Patients were divided into propensity score quintiles and linear regression models were constructed to determine the treatment effect sizes and confidence intervals. Results: From the 1082 patients that met entry criteria, 453 patients (41.9%) received ET. Those patients receiving ET showed significantly better scores on the EQ5D index, PHQ9, and MSPS, but only in the upper three propensity quintiles. For the T25FW, ET did not result in significantly better times in any quintile. Conclusions: These results suggest that ET of MS is beneficial but the effect appears modest.
VEGFR1 stimulates a CXCR4-dependent translocation of megakaryocytes to the vascular niche, enhancing platelet production in mice
Authors: Pitchford Simon C. , Lodie Tracey , Rankin Sara M. 
Published: June 2012

Abstract
It has previously been reported that VEGF-A stimulates megakaryocyte (MK) maturation in vitro. Here we show that treatment of mice with the isoform VEGF-A165 resulted in a significant increase in circulating numbers of platelets. Using specific VEGFR1 and VEGFR2 blocking mAbs and selective VEGFR1 and 2 agonists, PlGF-2 and VEGF-E, respectively, we show directly that stimulation of VEGFR1, but not VEGFR2, increases circulating platelet numbers in vivo. Using flow cytometric analysis of harvested MKs, we show that while PlGF does not change the absolute numbers of MKs present in the bone marrow and the spleen, it increases both their maturation and cell-surface expression of CXCR4 in the bone marrow. Histology of the bone marrow revealed a redistribution of MKs from the endosteal to the vascular niche in response to both VEGF-A165 and PlGF-2 treatment in vivo. Antagonism of CXCR4 suppressed both the VEGFR1-stimulated redistribution of megakyocytes within the bone marrow compartment and the VEGF-A165–induced thrombocytosis. In conclusion, we define a novel proinflammatory VEGFR1-mediated pathway that stimulates the maturation and up-regulation of CXCR4 on megakaryocytes, leading to their redistribution within the bone marrow environment, thereby enhancing platelet production in vivo.
Coagulation biomarkers predict disease progression in SIV-infected nonhuman primates
Authors: Pandrea Ivona , Cornell Elaine , Wilson Cara , Ribeiro Ruy M. , Ma Dongzhu , Kristoff Jan , Xu Cuiling , Haret-Richter George S. , Trichel Anita , Apetrei Cristian , Landay Alan , Tracy Russell 
Published: June 2012

AbstractHIV infection is associated with increased risk of cardiovascular complications, the underlying mechanism of which remains unclear. Plasma levels of the coagulation biomarker D-dimer (DD) correlate with increased mortality and cardiovascular events in HIV-infected patients. We compared the incidence of cardiovascular lesions and the levels of the coagulation markers DD and thrombin antithrombin in pathogenic SIV infections of rhesus and pigtailed macaques (PTMs) and in nonpathogenic SIV infection of African green monkeys (AGMs) and sooty mangabeys. Hypercoagulability and cardiovascular pathology were only observed in pathogenic SIV infections. In PTMs infected with SIV from AGMs (SIVagm), DD levels were highly indicative of AIDS progression and increased mortality and were associated with cardiovascular lesions, pointing to SIVagm-infected PTMs as an ideal animal model for the study of HIV-associated cardiovascular disease. In pathogenic SIV infection, DD increased early after infection, was strongly correlated with markers of immune activation/inflammation and microbial translocation (MT), and was only peripherally associated with viral loads. Endotoxin administration to SIVagm-infected AGMs (which lack chronic SIV-induced MT and immune activation) resulted in significant increases of DD. Our results demonstrate that hypercoagulation and cardiovascular pathology are at least in part a consequence of excessive immune activation and MT in SIV infection.