bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increasing doxorubicin activity against breast cancer cells using PPARγ‐ligands and by exploiting circadian rhythms
Authors: Arif I S , Hooper C L , Greco F , Williams A C , Boateng S Y 
Published: April 2013

Background and PurposeDoxorubicin is effective against breast cancer, but its major side effect is cardiotoxicity. The aim of this study was to determine whether the efficacy of doxorubicin on cancer cells could be increased in combination with PPARγ agonists or chrono‐optimization by exploiting the diurnal cycle.Experimental ApproachWe determined cell toxicity using MCF‐7 cancer cells, neonatal rat cardiac myocytes and fibroblasts in this study.Key ResultsDoxorubicin damages the contractile filaments of cardiac myocytes and affects cardiac fibroblasts by significantly inhibiting collagen production and proliferation at the level of the cell cycle. Cyclin D1 protein levels decreased significantly following doxorubicin treatment indicative of a G1/S arrest. PPARγ agonists with doxorubicin increased the toxicity to MCF‐7 cancer cells without affecting cardiac cells. Rosiglitazone and ciglitazone both enhanced anti‐cancer activity when combined with doxorubicin (e.g. 50% cell death for doxorubicin at 0.1 μM compared to 80% cell death when combined with rosiglitazone). Thus, the therapeutic dose of doxorubicin could be reduced by 20‐fold through combination with the PPARγ agonists, thereby reducing adverse effects on the heart. The presence of melatonin also significantly increased doxorubicin toxicity, in cardiac fibroblasts (1 μM melatonin) but not in MCF‐7 cells.Conclusions and ImplicationsOur data show, for the first time, that circadian rhythms play an important role in doxorubicin toxicity in the myocardium; doxorubicin should be administered mid‐morning, when circulating levels of melatonin are low, and in combination with rosiglitazone to increase therapeutic efficacy in cancer cells while reducing the toxic effects on the heart.
A Serious New Threat to Brazilian Freshwater Ecosystems: The Naturalization of Nonnative Fish by Decree
Authors: Pelicice Fernando Mayer , Vitule Jean Ricardo Simões , Lima Junior Dilermando Pereira , Orsi Mário Luis , Agostinho Angelo Antonio 
Published: April 2013

AbstractAs Brazil undergoes rapid economic growth, short‐sighted political decisions can threaten biological diversity and ecosystem services. Recently, the Brazilian Congress proposed a law to allow the rearing of nonnative fish in aquaculture cages in any hydroelectric reservoir of the country. This initiative may “naturalize by decree” some of the worst invasive species in the world (e.g., carps and tilapias) as a means of developing inland aquaculture and economy. The spread of aquaculture facilities will create opportunities for fish invasions to occur throughout the country, with the risk of damaging native biodiversity, ecosystem services, and environmental quality on a continental scale. The proposal ignores ecological theory, historical and/or empirical data concerning fish invasion, including dispersal, establishment, propagule pressure, invasiveness and invasibility, and all the negative consequences that may follow the invasion and establishment of nonnative organisms. This situation inspires reflection about the future of tropical biodiversity worldwide, particularly because Brazil, like many other developing countries, possesses a remarkable diversity of fish and other freshwater organisms yet has taken some political measures that are in conflict with important conservation issues.
In silico cloning and annotation of genes involved in the digestion, detoxification and RNA interference mechanism in the midgut of Bactrocera dorsalis [Hendel (Diptera: Tephritidae)]
Authors: Shen G.‐M. , Dou W. , Huang Y. , Jiang X.‐Z. , Smagghe G. , Wang J.‐J. 
Published: April 2013

AbstractAs the second largest organ in insects, the insect midgut is the major tissue involved in the digestion of food and detoxification of xenobiotics, such as insecticides, and the first barrier and target for oral RNA interference (RNAi). In this study, we performed a midgut‐specific transcriptome analysis in the oriental fruit fly, Bactrocera dorsalis, an economically important worldwide pest, with many populations showing high levels of insecticide resistance. Using high‐throughput sequencing, 52 838 060 short reads were generated and assembled to 25 236 unigenes with a mean length of 758 bp. Interestingly, 34 unique sequences encoding digestion enzymes were newly described and these included aminopeptidase and trypsin, genes associated with Bacillus thuringiensis resistance and fitness cost. Second, 41 transcripts were annotated to particular detoxification genes such as glutathione S‐transferases, carboxylesterases and cytochrome P450s, and the subsequent phylogenetic analysis indicated homology with tissue‐specific and insecticide resistance‐related genes of Drosophila melanogaster. Third, we identified the genes involved in the mechanism of RNAi and the uptake of double‐stranded RNA. The sequences encoding Dicer‐2, R2D2, AGO2, and Eater were confirmed, but SID and SR‐CI were absent in the midgut transcriptome. In conclusion, the results provide basic molecular information to better understand the mechanisms of food digestion, insecticide resistance and oral RNAi in this important pest insect in agriculture. Specific genes in these systems can be used in the future as potential targets for pest control, for instance, with RNAi technology.
Anti‐Gal: an abundant human natural antibody of multiple pathogeneses and clinical benefits
Authors: Galili Uri 
Published: April 2013

SummaryAnti‐Gal is the most abundant natural antibody in humans, constituting ~ 1% of immunoglobulins. Anti‐Gal is naturally produced also in apes and Old World monkeys. The ligand of anti‐Gal is a carbohydrate antigen called the ‘α‐gal epitope’ with the structure Galα1‐3Galβ1‐4GlcNAc‐R. The α‐gal epitope is present as a major carbohydrate antigen in non‐primate mammals, prosimians and New World monkeys. Anti‐Gal can contributes to several immunological pathogeneses. Anti‐Gal IgE produced in some individuals causes allergies to meat and to the therapeutic monoclonal antibody cetuximab, all presenting α‐gal epitopes. Aberrant expression of the α‐gal epitope or of antigens mimicking it in humans may result in autoimmune processes, as in Graves' disease. α‐Gal epitopes produced by Trypanosoma cruzi interact with anti‐Gal and induce ‘autoimmune like’ inflammatory reactions in Chagas' disease. Anti‐Gal IgM and IgG further mediate rejection of xenografts expressing α‐gal epitopes. Because of its abundance, anti‐Gal may be exploited for various clinical uses. It increases immunogenicity of microbial vaccines (e.g. influenza vaccine) presenting α‐gal epitopes by targeting them for effective uptake by antigen‐presenting cells. Tumour lesions are converted into vaccines against autologous tumour‐associated antigens by intra‐tumoral injection of α‐gal glycolipids, which insert into tumour cell membranes. Anti‐Gal binding to α‐gal epitopes on tumour cells targets them for uptake by antigen‐presenting cells. Accelerated wound healing is achieved by application of α‐gal nanoparticles, which bind anti‐Gal, activate complement, and recruit and activate macrophages that induce tissue regeneration. This therapy may be of further significance in regeneration of internally injured tissues such as ischaemic myocardium and injured nerves.
Cardiovascular effects of particulate air pollution exposure: time course and underlying mechanisms
Authors: Langrish J. P. , Bosson J. , Unosson J. , Muala A. , Newby D. E. , Mills N. L. , Blomberg A. , Sandström T. 
Published: April 2013

AbstractObjectiveAir pollution is now recognized as an important independent risk factor for cardiovascular morbidity and mortality and may be responsible for up to 3 million premature deaths each year worldwide. The mechanisms underlying the observed effects are poorly understood but are likely to be multifactorial. Here, we review the acute and chronic effects of air pollution exposure on the cardiovascular system and discuss how these effects may explain the observed increases in cardiovascular morbidity and mortality.
Adherence to a Mediterranean dietary pattern in early life is associated with lower arterial stiffness in adulthood: the Amsterdam Growth and Health Longitudinal Study
Authors: van de Laar R. J. J. , Stehouwer C. D. A. , van Bussel B. C. T. , Prins M. H. , Twisk J. W. R. , Ferreira I. 
Published: April 2013

AbstractObjectivesTo investigate whether adherence to a Mediterranean dietary pattern during adolescence and early adulthood affects arterial stiffness in adulthood, and the extent to which any such association may be attributed to a beneficial impact of this diet on cardiovascular disease risk factors such as blood pressure, central fatness and dyslipidaemia.SettingThe Amsterdam Growth and Health Longitudinal Study.Design and subjectsWe compared longitudinal levels of adherence to a Mediterranean dietary pattern (aMED score with range 0–9) during adolescence and adulthood (two to eight repeated measures obtained between the ages of 13 and 36) between individuals with different levels of arterial stiffness in adulthood. The study population included 373 (196 women) apparently healthy adults in whom properties of the carotid, brachial and femoral arteries were assessed using ultrasonography at 36 years of age.ResultsAfter adjustments for potential confounders, individuals with stiffer carotid arteries (defined on the basis of the most adverse tertile of, for instance, the distensibility coefficient) had lower aMED scores (−0.32, 95% CI −0.60; −0.06) and were less likely to have adhered to this dietary pattern (aMED score ≥5, odds ratio 0.69, 95% CI 0.50; −0.94) during the preceding 24 years compared with those with less stiff arteries. Differences in aMED scores were already present in adolescence and were only in part explained by the favourable associations between the Mediterranean dietary pattern and other cardiovascular disease risk factors (up to 26%), particularly mean blood pressure (up to 19%).ConclusionsPromoting the Mediterranean diet in adolescence and early adulthood may constitute an important means of preventing arterial stiffness in adulthood.
Cardiac resynchronization therapy: a breakthrough in heart failure management
Authors: Ståhlberg M. , Lund L. H. , Zabarovskaja S. , Gadler F. , Braunschweig F. , Linde C. 
Published: April 2013

AbstractHeart failure is now considered an epidemic. In patients with heart failure, electrical and mechanical dyssynchrony, evident primarily as prolongation of the QRS‐complex on the surface electrocardiogram, is associated with detrimental effects on the cardiovascular system at several levels. In the past 10 years, studies have demonstrated that by stimulating both cardiac ventricles simultaneously, or almost simultaneously [cardiac resynchronization therapy (CRT)], the adverse effects of dyssynchrony can be overcome. Here, we provide a comprehensive overview of different aspects of CRT including the rationale behind and evidence for efficacy of the therapy. Issues with regard to gender effects and patient follow‐up as well as a number of unresolved concerns will also be discussed.
Oxidized LDL level is related to gene expression of tumour necrosis factor super family members in children and young adults with familial hypercholesterolaemia
Authors: Narverud I. , Halvorsen B. , Nenseter M. S. , Retterstøl K. , Yndestad A. , Dahl T. B. , Ulven S. M. , Olstad O. K. , Ose L. , Holven K. B. , Aukrust P. 
Published: April 2013

AbstractObjectiveFamilial hypercholesterolaemia (FH) is associated with increased risk of premature atherosclerosis. Inflammation is a key event in atherogenesis, and we have previously reported an inflammatory imbalance between tumour necrosis factor (TNF)α and interleukin‐10 in children with FH. Based on the potential role of TNF‐related molecules in inflammation, we investigated the regulation of other members of the TNF superfamily (TNFSF)/TNF receptor superfamily (TNFRSF) in children and young adults with FH and matched healthy controls.MethodsExpression of TNFSF/TNFRSF genes in peripheral blood mononuclear cells (PBMCs) was quantified in children and young adults with FH prior to (n = 42) and after statin treatment (n = 10) and in controls (n = 25) by quantitative real‐time polymerase chain reaction.ResultsFirst we found that, compared with controls, the mRNA levels of OX40L, BAFFR and TRAILR1 were significantly higher, whereas TRAIL and TRAILR3 were significantly lower in children and young adults with FH. Secondly, levels of oxidized low‐density lipoprotein (oxLDL) were significantly raised in the FH group, and correlated with the expression of OX40L, BAFFR and TRAILR1. Thirdly, oxLDL increased mRNA levels of BAFFR, TRAILR1 and TRAILR4 in PBMCs ex vivo from individuals with FH. Fourthly, OX40, acting through OX40L, enhanced the oxLDL‐induced expression of matrix metalloproteinase‐9 in THP‐1 monocytes in vitro. Finally, after statin treatment in children with FH (n = 10), mRNA levels of OX40L and TRAILR1 decreased, whereas levels BAFF, TRAIL and TRAILR3 increased.ConclusionOur findings suggest the involvement of some TNFSF/TNFRSF members and oxLDL in the early stages of atherogenesis; this may potentially contribute to the accelerated rate of atherosclerosis observed in individuals with FH.
Identifying novel biomarkers for cardiovascular disease risk prediction
Authors: Ge Y. , Wang T. J. 
Published: April 2013

AbstractThe primary prevention of cardiovascular disease relies on the ability to identify at‐risk individuals long before the development of overt events. In the past decade, research into circulating, genetic and imaging biomarkers to augment traditional methods of risk prediction has only achieved modest success. Emerging technologies in the fields of genomics, metabolomics and proteomics are providing new platforms for biomarker discovery. Here, we review current concepts in the evaluation and discovery of cardiovascular biomarkers. Further research is needed to identify new biomarkers to successfully stratify risk of cardiovascular disease in low‐risk populations, as well as to test whether management strategies informed by biomarker testing are better than standard of care.
Cardiovascular disease event rates in patients with severe psoriasis treated with systemic anti‐inflammatory drugs: a Danish real‐world cohort study
Authors: Ahlehoff O. , Skov L. , Gislason G. , Lindhardsen J. , Kristensen S. L. , Iversen L. , Lasthein S. , Gniadecki R. , Dam T. N. , Torp‐Pedersen C. , Hansen P. R. 
Published: April 2013

AbstractObjectivesPsoriasis is a chronic inflammatory disorder associated with cardiovascular morbidity and mortality. Systemic anti‐inflammatory drugs, including biological agents, are widely used in the treatment of patients with moderate to severe psoriasis and may attenuate the risk of cardiovascular disease events. We therefore examined the rate of cardiovascular disease events in patients with severe psoriasis treated with systemic anti‐inflammatory drugs.Design, setting and participantsIndividual‐level linkage of nationwide administrative databases was used to assess the event rates associated with use of biological agents, methotrexate or other therapies, including retinoids, cyclosporine and phototherapy, in Denmark from 2007 to 2009.Main outcome measureDeath, myocardial infarction and stroke.ResultsA total of 2400 patients with severe psoriasis, including 693 patients treated with biological agents and 799 treated with methotrexate, were identified. Incidence rates per 1000 patient‐years and 95% confidence intervals (CIs) for the composite endpoint were 6.0 (95% CI 2.7–13.4), 17.3 (95% CI 12.3–24.3) and 44.5 (95% CI 34.6–57.0) for patients treated with biological agents, methotrexate and other therapies, respectively. Age‐ and sex‐adjusted hazard ratios (HRs) were 0.28 (95% CI 0.12–0.64) and 0.65 (95% CI 0.42–1.00) for patients treated with biological agents and methotrexate, respectively, using other therapies as the reference cohort. Corresponding HRs for a secondary composite endpoint of cardiovascular death, myocardial infarction and stroke were 0.48 (95% CI 0.17–1.38) and 0.50 (95% CI 0.26–0.97).ConclusionIn this nationwide study of patients with severe psoriasis, systemic anti‐inflammatory treatment with biological agents or methotrexate was associated with lower cardiovascular disease event rates compared to patients treated with other anti‐psoriatic therapies.
‘Being there’: the Experiences of Staff in Dealing with Matters of Dying and Death in Services for People with Intellectual Disabilities
Authors: Todd Stuart 
Published: April 2013

BackgroundResearch on staffed housing for people with intellectual disability has identified the challenges in achieving postitive quality of life outcomes. However, a less well considered dimension of such services is that they are places of living and dying. This paper looks at the experiences of staff in dealing with issues of death and dying.MethodIn depth qualitative interviews were held with 22 staff in 5 different providers and who had experienced, in total, 27 deaths of people with intellectual disability.ResultsThe data highlight that staff felt providing a good quality of care at the end of life was an important but unrecognised dimension of their work. This work could be broken down into several different phases, dying, death and beyond death. Bad deaths were felt to be those deaths which prevented staff from ‘being there’ with individuals over those phases.
From southern refugia to the northern range margin: genetic population structure of the common wall lizard, Podarcis muralis
Authors: Gassert Franz , Schulte Ulrich , Husemann Martin , Ulrich Werner , Rödder Dennis , Hochkirch Axel , Engel Edmée , Meyer Jobst , Habel Jan Christian 
Published: April 2013

AbstractAimThermophilic species persisted in southern refugia during the cold phases of the Pleistocene, and expanded northwards during warming. These processes caused genetic imprints, such as a differentiation of genetic lineages and a loss of genetic diversity in the wake of (re)colonization. We used molecular markers and species distribution models (SDMs) to study the impact of range dynamics on the common wall lizard, Podarcis muralis, from southern refugia to the northern range margin.LocationParts of the Western Palaearctic.MethodsWe genotyped 10 polymorphic microsatellites in 282 individuals of P. muralis and sequenced the mitochondrial DNA (mtDNA) cytochrome b gene to study the genetic structure, divergence times and ancestral distributions. Furthermore, we generated SDMs for climate scenarios for 6 and 21 ka derived from two different global circulation models.ResultsWe detected two major mtDNA lineages – a western France clade (Pyrenees to Brittany), and an eastern France clade (southern France to Germany, Belgium and Luxembourg). This split was dated to c. 1.23 Ma. The latter clade was divided into two subclades, which diverged c. 0.38 Ma. Genetic diversity of microsatellites within each clade was nested and showed a significant loss of genetic diversity from south to north, a strong pattern of allele surfing across nearly all loci, and an increase in genetic differentiation towards the northern range margin. Results from SDMs suggest that southward range retraction during the late glacial period split the distribution into geographically distinct refugia.Main conclusionsThe strong genetic differentiation mirrors the effects of long‐term isolation of P. muralis in multiple refugia. Post‐glacial recolonization of Northern Europe has taken place from two distinct refugia, most probably along river systems (Rhône, Rhine, Moselle) and along the Atlantic coastline, with subsequent nested elimination of genetic diversity and increasing genetic differentiation at the northern range margin.
Long‐term mTOR inhibitors administration evokes altered calcium homeostasis and platelet dysfunction in kidney transplant patients
Authors: López Esther , Berna‐Erro Alejandro , Bermejo Nuria , Brull José María , Martinez Rocío , Garcia Pino Guadalupe , Alvarado Raul , Salido Ginés María , Rosado Juan Antonio , Cubero Juan José , Redondo Pedro Cosme 
Published: April 2013

AbstractThe use of the mammal target of rapamycin (mTOR) inhibitors has been consolidated as the therapy of election for preventing graft rejection in kidney transplant patients, despite their immunosuppressive activity is less strong than anti‐calcineurin agents like tacrolimus and cyclosporine A. Furthermore, as mTOR is widely expressed, rapamycin (a macrolide antibiotic produced by Streptomyces hygroscopicus) is recommended in patients presenting neoplasia due to its antiproliferative actions. Hence, we have investigated whether rapamycin presents side effects in the physiology of other cell types different from leucocytes, such as platelets. Blood samples were drawn from healthy volunteers and kidney transplant patients long‐term medicated with rapamycin: sirolimus and everolimus. Platelets were either loaded with fura‐2 or directly stimulated, and immunoassayed or fixed with Laemmli's buffer to perform the subsequent analysis of platelet physiology. Our results indicate that rapamycin evokes a biphasic time‐dependent alteration in calcium homeostasis and function in platelets from kidney transplant patients under rapamycin regime, as demonstrated by the reduction in granule secretion observed and subsequent impairment of platelet aggregation in these patients compared with healthy volunteers. Platelet count was also reduced in these patients, thus 41% of patients presented thrombocytopenia. All together our results show that long‐term administration of rapamycin to kidney transplant patients evokes alteration in platelet function.
Managing anticoagulation for atrial fibrillation: current issues and future strategies
Authors: John Camm A. 
Published: April 2013

AbstractAlthough warfarin is superior to aspirin in reducing the risk of stroke in patients with atrial fibrillation, it can increase major bleeds. Hence, physicians stratify patients according to stroke risk to ensure a net benefit. In this review, the CHA2DS2‐VASc stratification scheme used in the latest European Society of Cardiology (2010/12) guidelines will be explained. The greater sensitivity of this scheme, compared to the previous CHADS2, more closely delineates patients for whom warfarin is appropriate. The review also anticipates that there will be a wider range of patients who may benefit from the new oral anticoagulants, which show similar or superior efficacy and/or safety to warfarin with a significant reduction in intracranial haemorrhage and do not require routine coagulation monitoring. The role of conventional and new anticoagulant options will also be discussed.