bluuebunny/crossref_metadata_2025_split huggingface dataset:
Wnt/beta-catenin signaling activates microRNA-181 expression in hepatocellular carcinoma
Authors: Ji Junfang , Yamashita Taro , Wang Xin W 
Published: January 2011

Abstract

Background
Hepatocellular carcinoma (HCC) is a malignant cancer with an observable heterogeneity and microRNAs are functionally associated with the tumorigenesis of HCC. We recently identified that EpCAM (CD326)-positive cells isolated from alpha-fetoprotein (AFP)-positive HCC samples are hepatic cancer stem cells (HepCSCs). EpCAM+AFP+ HepCSCs have an activated Wnt/β-catenin signaling with a parallel increased expression of all four microRNA-181 family members. We hypothesized that Wnt/β-catenin signaling transcriptionally activates microRNA-181s in HCC.

Results
Using both western blot and quantitative reverse transcriptase-PCR analyses, we found that the expression of all four microRNA-181 family members was positively correlated with β-catenin expression in HCC cell lines. MicroRNA-181 expression could be directly induced upon an activation of Wnt/β-catenin signaling, which includes Wnt10B overexpression, inhibition of GSK3β signaling by LiCl, or forced expression of β-catenin/Tcf4. Moreover, microRNA-181 expression was inhibited upon an inactivation of Wnt/β-catenin signaling by an induction of adenomatosis polyposis coli (APC) expression or silencing β-catenin via RNA interference. In addition, seven putative β-catenin/Tcf4 binding sites were identified in the promoter region of the microRNA-181a-2 and microRNA-181b-2 transcripts. Consistently, we found that Tcf4 interacted with these regions in vivo using chromatin immunoprecipitation assay.

Conclusions
Taken together, our results demonstrate that microRNA-181s are transcriptionally activated by the Wnt/beta-catenin signaling pathway in HCC.
Transcriptome signature of the adult mouse choroid plexus
Authors: Marques Fernanda , Sousa João C , Coppola Giovanni , Gao Fuying , Puga Renato , Brentani Helena , Geschwind Daniel H , Sousa Nuno , Correia-Neves Margarida , Palha Joana A 
Published: January 2011

Abstract

Background
Although the gene expression profile of several tissues in humans and in rodent animal models has been explored, analysis of the complete choroid plexus (CP) transcriptome is still lacking. A better characterization of the CP transcriptome can provide key insights into its functions as one of the barriers that separate the brain from the periphery and in the production of cerebrospinal fluid.

Methods
This work extends further what is known about the mouse CP transcriptome through a microarray analysis of CP tissue from normal mice under physiological conditions.

Results
We found that the genes most highly expressed are those implicated in energy metabolism (oxidative phosphorylation, glycolysis/gluconeogenesis) and in ribosomal function, which is in agreement with the secretory nature of the CP. On the other hand, genes encoding for immune mediators are among those with lower expression in basal conditions. In addition, we found genes known to be relevant during brain development, and not previously identified to be expressed in the CP, including those encoding for various axonal guidance and angiogenesis molecules and for growth factors. Some of these are known to influence the neural stem cell niche in the subventricular zone, highlighting the involvement of the CP as a likely modulator of neurogenesis. Interestingly, our observations confirm that the CP transcriptome is unique, displaying low homology with that of other tissues. Of note, we describe here that the closest similarity is with the transcriptome of the endothelial cells of the blood-brain barrier.

Conclusions
Based on the data presented here, it will now be possible to further explore the function of particular proteins of the CP secretome in health and in disease.
The CNS microvascular pericyte: pericyte-astrocyte crosstalk in the regulation of tissue survival
Authors: Bonkowski Drew , Katyshev Vladimir , Balabanov Roumen D , Borisov Andre , Dore-Duffy Paula 
Published: January 2011

AbstractThe French scientist Charles Benjamin Rouget identified the pericyte nearly 140 years ago. Since that time the role of the pericyte in vascular function has been difficult to elucidate. It was not until the development of techniques to isolate and culture pericytes that scientists have begun to understand the true impact of this unique cell in the maintenance of tissue homeostasis. In the brain the pericyte is an integral cellular component of the blood-brain barrier and, together with other cells of the neurovascular unit (endothelial cells, astrocytes and neurons) the pericyte makes fine-tuned regulatory adjustments and adaptations to promote tissue survival. These regulatory changes involve trans-cellular communication networks between cells. In this review we consider evidence for cell-to-cell crosstalk between pericytes and astrocytes during development and in adult brain.
Toll-like receptor 3 upregulation by type I interferon in healthy and scleroderma dermal fibroblasts
Authors: Agarwal Sandeep K , Wu Minghua , Livingston Christopher K , Parks Donald H , Mayes Maureen D , Arnett Frank C , Tan Filemon K 
Published: January 2011

Abstract
Introduction
Increased levels of genes in the type I interferon (IFN) pathway have been observed in patients with systemic sclerosis (SSc), or scleroderma. How type I IFN regulates the dermal fibroblast and its participation in the development of dermal fibrosis is not known. We hypothesized that one mechanism by which type I IFN may contribute to dermal fibrosis is through upregulation of specific Toll-like receptors (TLRs) on dermal fibroblasts. Therefore, we investigated the regulation of TLR expression on dermal fibroblasts by IFN.

Methods
The expression of TLRs was assessed in cultured dermal fibroblasts from control and SSc patients stimulated with IFNα2. The ability of IFNα2 to regulate TLR-induced interleukin (IL)-6 and CC chemokine ligand 2 production was also assessed. Immunohistochemical analyses were performed to determine whether TLR3 was expressed in skin biopsies in the bleomycin-induced skin fibrosis model and in patients with SSc.

Results
IFNα2 increased TLR3 expression on human dermal fibroblasts, which resulted in enhanced TLR3-induced IL-6 production. SSc fibroblasts have an augmented TLR3 response to IFNα2 relative to control fibroblasts. Pretreatment of fibroblasts with transforming growth factor (TGF)-β increased TLR3 induction by IFNα2, but coincubation of TGF-β did not alter TLR3 induction by IFN. Furthermore, IFNα2 inhibits but does not completely block the induction of connective tissue growth factor and collagen expression by TGF-βin fibroblasts. TLR3 expression was observed in dermal fibroblasts and inflammatory cells from skin biopsies from patients with SSc as well as in the bleomycin-induced skin fibrosis model.

Conclusions
Type I IFNs can increase the inflammatory potential of dermal fibroblasts through the upregulation of TLR3.
A p53-independent role of Mdm2 in estrogen-mediated activation of breast cancer cell proliferation
Authors: Brekman Angelika , Singh Kathryn E , Polotskaia Alla , Kundu Nandini , Bargonetti Jill 
Published: January 2011

Abstract
Introduction
Estrogen receptor positive breast cancers often have high levels of Mdm2. We investigated if estrogen signaling in such breast cancers occurred through an Mdm2 mediated pathway with subsequent inactivation of p53.

Methods
We examined the effect of long-term 17β-estradiol (E2) treatment (five days) on the p53-Mdm2 pathway in estrogen receptor alpha (ERα) positive breast cancer cell lines that contain wild-type p53 (MCF-7 and ZR75-1). We assessed the influence of estrogen by examining cell proliferation changes, activation of transcription of p53 target genes, p53-chromatin interactions and cell cycle profile changes. To determine the effects of Mdm2 and p53 knockdown on the estrogen-mediated proliferation signals we generated MCF-7 cell lines with inducible shRNA for mdm2 or p53 and monitored their influence on estrogen-mediated outcomes. To further address the p53-independent effect of Mdm2 in ERα positive breast cancer we generated cell lines with inducible shRNA to mdm2 using the mutant p53 expressing cell line T-47D.

Results
Estrogen increased the Mdm2 protein level in MCF-7 cells without decreasing the p53 protein level. After estrogen treatment of MCF-7 cells, down-regulation of basal transcription of p53 target genes puma and p21 was observed. Estrogen treatment also down-regulated etoposide activated transcription of puma, but not p21. Mdm2 knockdown in MCF-7 cells increased p21 mRNA and protein, decreased cell growth in 3D matrigel and also decreased estrogen-induced cell proliferation in 2D culture. In contrast, knockdown of p53 had no effect on estrogen-induced cell proliferation. In T-47D cells with mutant p53, the knockdown of Mdm2 decreased estrogen-mediated cell proliferation but did not increase p21 protein.

Conclusions
Estrogen-induced breast cancer cell proliferation required a p53-independent role of Mdm2. The combined influence of genetic and environmental factors on the tumor promoting effects of estrogen implicated Mdm2 as a strong contributor to the bypass of cell cycle checkpoints. The novel finding that p53 was not the key target of Mdm2 in the estrogen activation of cell proliferation could have great benefit for future Mdm2-targeted breast cancer therapies.
Clinical accuracy of RIFLE and Acute Kidney Injury Network (AKIN) criteria for acute kidney injury in patients undergoing cardiac surgery
Authors: Englberger Lars , Suri Rakesh M , Li Zhuo , Casey Edward T , Daly Richard C , Dearani Joseph A , Schaff Hartzell V 
Published: January 2011

Abstract
Introduction
The RIFLE (risk, injury, failure, loss of kidney function, and end-stage renal failure) classification for acute kidney injury (AKI) was recently modified by the Acute Kidney Injury Network (AKIN). The two definition systems differ in several aspects, and it is not clearly determined which has the better clinical accuracy.

Methods
In a retrospective observational study we investigated 4,836 consecutive patients undergoing cardiac surgery with cardiopulmonary bypass from 2005 to 2007 at Mayo Clinic, Rochester, MN, USA. AKI was defined by RIFLE and AKIN criteria.

Results
Significantly more patients were diagnosed as AKI by AKIN (26.3%) than by RIFLE (18.9%) criteria (P < 0.0001). Both definitions showed excellent association to outcome variables with worse outcome by increased severity of AKI (P < 0.001, all variables). Mortality was increased with an odds ratio (OR) of 4.5 (95% CI 3.6 to 5.6) for one class increase by RIFLE and an OR of 5.3 (95% CI 4.3 to 6.6) for one stage increase by AKIN. The multivariate model showed lower predictive ability of RIFLE for mortality. Patients classified as AKI in one but not in the other definition set were predominantly staged in the lowest AKI severity class (9.6% of patients in AKIN stage 1, 2.3% of patients in RIFLE class R). Potential misclassification of AKI is higher in AKIN, which is related to moving the 48-hour diagnostic window applied in AKIN criteria only. The greatest disagreement between both definition sets could be detected in patients with initial postoperative decrease of serum creatinine.

Conclusions
Modification of RIFLE by staging of all patients with acute renal replacement therapy (RRT) in the failure class F may improve predictive value. AKIN applied in patients undergoing cardiac surgery without correction of serum creatinine for fluid balance may lead to over-diagnosis of AKI (poor positive predictive value). Balancing limitations of both definition sets of AKI, we suggest application of the RIFLE criteria in patients undergoing cardiac surgery.
Antibiotics or probiotics as preventive measures against ventilator-associated pneumonia: a literature review
Authors: Schultz Marcus J , Haas Lenneke E 
Published: January 2011

Abstract
Introduction
Mechanically ventilated critically ill patients frequently develop ventilator-associated pneumonia (VAP), a life-threatening complication. Proposed preventive measures against VAP include, but are not restricted to, selective decontamination of the digestive tract (SDD), selective oropharyngeal decontamination (SOD) and the use of probiotics. Probiotics are live bacteria that could have beneficial effects on the host by altering gastrointestinal flora. Similar to SDD and SOD, a prescription of probiotics aims at the prevention of secondary colonization of the upper and/or lower digestive tract.

Methods
We performed a literature review to describe the differences and similarities between SDD/SOD and probiotic preventive strategies, focusing on (a) efficacy, (b) risks, and (c) the routing of these strategies.

Results
Reductions in the incidence of VAP have been achieved with SDD and SOD. Two large randomized controlled trials even showed reduced mortality with these preventive strategies. Randomized controlled trials of probiotic strategies also showed a reduction of the incidence of VAP, but trials were too small to draw firm conclusions. Preventive strategies with antibiotics and probiotics may be limited due to the risk of emerging resistance to the locally applied antibiotics and the risk of probiotic-related infections, respectively. The majority of trials of SDD and SOD did not exhaustively address the issue of emerging resistance. Likewise, trials of probiotic strategies did not adequately address the risk of colonization with probiotics and probiotic-related infection. In studies of SDD and SOD the preventive strategy aimed at decontamination of the oral cavity, throat, stomach and intestines, and the oral cavity and throat, respectively. In the vast majority of studies of probiotic therapy the preventive strategy aimed at decontamination of the stomach and intestines.

Conclusions
Prophylactic use of antibiotics in critically ill patients is effective in reducing the incidence of VAP. Probiotic strategies deserve consideration in future well-powered trials. Future studies are needed to determine if preventive antibiotic and probiotic strategies are safe with regard to development of antibiotic resistance and probiotic infections. It should be determined whether the efficacy of probiotics improves when these agents are provided to the mouth and the intestines simultaneously.
Endogenous plasma activated protein C levels and the effect of enoxaparin and drotrecogin alfa (activated) on markers of coagulation activation and fibrinolysis in pulmonary embolism
Authors: Dempfle Carl-Erik H , Elmas Elif , Link Andreas , Suvajac Nenad , Liebe Volker , Janes Jonathan , Borggrefe Martin 
Published: January 2011

Abstract
Introduction
There are no published data on the status of endogenous activated protein C (APC) in pulmonary embolism (PE), and no data on the effect of drotrecogin alfa (activated) (DAA) given in addition to therapeutic dose enoxaparin.

Methods
In this double-blind clinical trial, 47 patients with computed tomography (CT)-confirmed acute submassive PE treated with 1 mg/kg body weight of enoxaparin twice daily were randomized to groups receiving a 12-hour intravenous infusion of 6, 12, 18, or 24 μg/kg/hour of DAA or a placebo. Blood samples were drawn before starting DAA infusion, after 4, 8 and 12 hours (at the end of the infusion period), and on treatment days 2, 3, 4, 5 and 6.

Results
Initial endogenous plasma activated protein C (APC) levels were 0.36 ± 0.48 ng/ml (<0.10 to 1.72 ng/ml) and remained in the same range in the placebo group. APC levels in patients treated with DAA were 13.67 ± 3.57 ng/ml, 32.71 ± 8.76 ng/ml, 36.13 ± 7.60 ng/ml, and 51.79 ± 15.84 ng/ml in patients treated with 6, 12, 18, and 24 μg/kg/hour DAA, respectively. In patients with a D-dimer level >4 mg/L indicating a high level of acute fibrin formation and dissolution, DAA infusion resulted in a more rapid drop in soluble fibrin, D-dimer, and fibrinogen/fibrin degradation products (FDP) levels, compared to enoxaparin alone. There was a parallel decline of soluble fibrin, D-dimer, FDP, and plasmin-plasmin inhibitor complex (PPIC) in response to treatment with enoxaparin ± DAA, with no evidence of a systemic profibrinolytic effect of the treatment.

Conclusions
In patients with acute submassive PE endogenous APC levels are low. DAA infusion enhances the inhibition of fibrin formation.

Trial registration
ClinicalTrials.gov: NCT00191724
Revisiting the value of pre-hospital tracheal intubation: an all time systematic literature review extracting the Utstein airway core variables
Authors: Lossius Hans Morten , Sollid Stephen JM , Rehn Marius , Lockey David J 
Published: January 2011

Abstract
Introduction
Although tracheal intubation (TI) in the pre-hospital setting is regularly carried out by emergency medical service (EMS) providers throughout the world, its value is widely debated. Heterogeneity in procedures, providers, patients, systems and stated outcomes, and inconsistency in data reporting make scientific reports difficult to interpret and compare, and the majority are of limited quality. To hunt down what is really known about the value of pre-hospital TI, we determined the rate of reported Utstein airway variables (28 core variables and 12 fixed-system variables) found in current scientific publications on pre-hospital TI.

Methods
We performed an all time systematic search according to the PRISMA guidelines of Medline and EMBASE to identify original research pertaining to pre-hospital TI in adult patients.

Results
From 1,076 identified records, 73 original papers were selected. Information was extracted according to an Utstein template for data reporting from in-the-field advanced airway management. Fifty-nine studies were from North American EMS systems. Of these, 46 (78%) described services in which non-physicians conducted TI. In 12 of the 13 non-North American EMS systems, physicians performed the pre-hospital TI. Overall, two were randomised controlled trials (RCTs), and 65 were observational studies. None of the studies presented the complete set of recommended Utstein airway variables. The median number of core variables reported was 10 (max 21, min 2, IQR 8-12), and the median number of fixed system variables was 5 (max 11, min 0, IQR 4-8). Among the most frequently reported variables were "patient category" and "service mission type", reported in 86% and 71% of the studies, respectively. Among the least-reported variables were "co-morbidity" and "type of available ventilator", both reported in 2% and 1% of the studies, respectively.

Conclusions
Core data required for proper interpretation of results were frequently not recorded and reported in studies investigating TI in adults. This makes it difficult to compare scientific reports, assess their validity, and extrapolate to other EMS systems. Pre-hospital TI is a complex intervention, and terminology and study design must be improved to substantiate future evidence based clinical practice.
Inhibition of caspase-1 activation in gram-negative sepsis and experimental endotoxemia
Authors: Giamarellos-Bourboulis Evangelos J , van de Veerdonk Frank L , Mouktaroudi Maria , Raftogiannis Maria , Antonopoulou Anastasia , Joosten Leo AB , Pickkers Peter , Savva Athina , Georgitsi Marianna , van der Meer Jos WM , Netea Mihai G 
Published: January 2011

Abstract
Introduction
Down-regulation of ex-vivo cytokine production is a specific feature in patients with sepsis. Cytokine downregulation was studied focusing on caspase-1 activation and conversion of pro-interleukin-1β into interleukin-1β (IL-1β).

Methods
Peripheral blood mononuclear cells were isolated from a) 92 patients with sepsis mainly of Gram-negative etiology; b) 34 healthy volunteers; and c) 5 healthy individuals enrolled in an experimental endotoxemia study. Cytokine stimulation was assessed in vitro after stimulation with a variety of microbial stimuli.

Results
Inhibition of IL-1β in sepsis was more profound than tumour necrosis factor (TNF). Down-regulation of IL-1β response could not be entirely explained by the moderate inhibition of transcription. We investigated inflammasome activation and found that in patients with sepsis, both pro-caspase-1 and activated caspase-1 were markedly decreased. Blocking caspase-1 inhibited the release of IL-1β in healthy volunteers, an effect that was lost in septic patients. Finally, urate crystals, which specifically induce the NLPR3 inflammasome activation, induced significant IL-1β production in healthy controls but not in patients with sepsis. These findings were complemented by inhibition of caspase-1 autocleavage as early as two hours after lipopolysaccharide exposure in volunteers.

Conclusions
These data demonstrate that the inhibition of caspase-1 and defective IL-1 β production is an important immunological feature in sepsis.
Impact of delayed admission to intensive care units on mortality of critically ill patients: a cohort study
Authors: Cardoso Lucienne TQ , Grion Cintia MC , Matsuo Tiemi , Anami Elza HT , Kauss Ivanil AM , Seko Ludmila , Bonametti Ana M 
Published: January 2011

Abstract
Introduction
When the number of patients who require intensive care is greater than the number of beds available, intensive care unit (ICU) entry flow is obstructed. This phenomenon has been associated with higher mortality rates in patients that are not admitted despite their need, and in patients that are admitted but are waiting for a bed. The purpose of this study is to evaluate if a delay in ICU admission affects mortality for critically ill patients.

Methods
A prospective cohort of adult patients admitted to the ICU of our institution between January and December 2005 were analyzed. Patients for whom a bed was available were immediately admitted; when no bed was available, patients waited for ICU admission. ICU admission was classified as either delayed or immediate. Confounding variables examined were: age, sex, originating hospital ward, ICU diagnosis, co-morbidity, Acute Physiology and Chronic Health Evaluation (APACHE) II score, therapeutic intervention, and Sequential Organ Failure Assessment (SOFA) score. All patients were followed until hospital discharge.

Results
A total of 401 patients were evaluated; 125 (31.2%) patients were immediately admitted and 276 (68.8%) patients had delayed admission. There was a significant increase in ICU mortality rates with a delay in ICU admission (P = 0.002). The fraction of mortality risk attributable to ICU delay was 30% (95% confidence interval (CI): 11.2% to 44.8%). Each hour of waiting was independently associated with a 1.5% increased risk of ICU death (hazard ratio (HR): 1.015; 95% CI 1.006 to 1.023; P = 0.001).

Conclusions
There is a significant association between time to admission and survival rates. Early admission to the ICU is more likely to produce positive outcomes.