bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential CARM1 expression in prostate and colorectal cancers
Authors: Kim Young-Rang , Lee Byung Kook , Park Ra-Young , Nguyen Nguyen Thi Xuan , Bae Jeong A , Kwon Dong Deuk , Jung Chaeyong 
Published: May 2010

AbstractBackgroundCoactivator-associated arginine methyltransferase 1 (CARM1) functions as a transcriptional coactivator of androgen receptor (AR)-mediated signaling. Correspondingly, overexpression of CARM1 has been associated with the development of prostate cancer (PCa) and its progression to androgen-independent PCa. In our preliminary study, however, the promoting effects of CARM1, with regard to androgen-stimulated AR target gene expression were minimal. These results suggested that the AR target gene expression associated with CARM1 may result primarily from non-hormone dependent activity. The goal of this study was to confirm the pattern of expression of CARM1 in human tumors and determine the mechanism of action in CARM1 overexpressed tumors.MethodsTissue microarray was used to determine the pattern of expression of CARM1 in human cancers by immunohistochemistry. CARM1 expression was also evaluated in prostate and colorectal surgical specimens and the clinical records of all cases were reviewed. In addition, a reporter transcription assay using the prostate-specific antigen (PSA) promoter was used to identify the signaling pathways involved in non-hormone-mediated signal activation associated with CARM1.ResultsThe tissue microarray showed that CARM1 was particularly overexpressed in the colorectal cancers while CARM1 expression was not prevalent in the prostate and breast cancers. Further studies using surgical specimens demonstrated that CARM1 was highly overexpressed in 75% of colorectal cancers (49 out of 65) but not in the androgen-independent PCa. In addition, CARM1's coactivating effect on the entire PSA promoter was very limited in both androgen-dependent and androgen-independent PCa cells. These results suggest that there are other factors associated with CARM1 expression in PSA regulation. Indeed, CARM1 significantly regulated both p53 and NF-κB target gene transcription.ConclusionsThe results of this study suggest that, in addition to its role in activation of steroid receptors, CARM1 functions as a transcriptional modulator by altering the activity of many transcriptional factors, especially with regard to androgen independent PCa and colorectal cancers.
Growth factors in multiple myeloma: a comprehensive analysis of their expression in tumor cells and bone marrow environment using Affymetrix microarrays
Authors: Mahtouk Karène , Moreaux Jérôme , Hose Dirk , Rème Thierry , Meißner Tobias , Jourdan Michel , Rossi Jean François , Pals Steven T , Goldschmidt Hartmut , Klein Bernard 
Published: May 2010

Abstract

Background
Multiple myeloma (MM) is characterized by a strong dependence of the tumor cells on their microenvironment, which produces growth factors supporting survival and proliferation of myeloma cells (MMC). In the past few years, many myeloma growth factors (MGF) have been described in the literature. However, their relative importance and the nature of the cells producing MGF remain unidentified for many of them.

Methods
We have analysed the expression of 51 MGF and 36 MGF receptors (MGFR) using Affymetrix microarrays throughout normal plasma cell differentiation, in MMC and in cells from the bone marrow (BM) microenvironment (CD14, CD3, polymorphonuclear neutrophils, stromal cells and osteoclasts).

Results
4/51 MGF and 9/36 MGF-receptors genes were significantly overexpressed in plasmablasts (PPC) and BM plasma cell (BMPC) compared to B cells whereas 11 MGF and 11 MGFR genes were overexpressed in BMPC compared to PPC. 3 MGF genes (AREG, NRG3, Wnt5A) and none of the receptors were significantly overexpressed in MMC versus BMPC. Furthermore, 3/51 MGF genes were overexpressed in MMC compared to the the BM microenvironment whereas 22/51 MGF genes were overexpressed in one environment subpopulation compared to MMC.

Conclusions
Two major messages arise from this analysis 1) The majority of MGF genes is expressed by the bone marrow environment. 2) Several MGF and their receptors are overexpressed throughout normal plasma cell differentiation. This study provides an extensive and comparative analysis of MGF expression in plasma cell differentiation and in MM and gives new insights in the understanding of intercellular communication signals in MM.
Platelet-activating factor receptor (PAF-R)-dependent pathways control tumour growth and tumour response to chemotherapy
Authors: de Oliveira Soraya I , Andrade Luciana NS , Onuchic Ana C , Nonogaki Sueli , Fernandes Patrícia D , Pinheiro Mônica C , Rohde Ciro BS , Chammas Roger , Jancar Sonia 
Published: May 2010

Abstract

Background
Phagocytosis of apoptotic cells by macrophages induces a suppressor phenotype. Previous data from our group suggested that this occurs via Platelet-activating factor receptor (PAF-R)-mediated pathways. In the present study, we investigated the impact of apoptotic cell inoculation or induction by a chemotherapeutic agent (dacarbazine, DTIC) on tumour growth, microenvironmental parameters and survival, and the effect of treatment with a PAF-R antagonist (WEB2170). These studies were performed in murine tumours: Ehrlich Ascitis Tumour (EAT) and B16F10 melanoma.

Methods
Tumour growth was assessed by direct counting of EAT cells in the ascitis or by measuring the volume of the solid tumour. Parameters of the tumour microenvironment, such as the frequency of cells expressing cyclo-oxygenase-2 (COX-2), caspase-3 and galectin-3, and microvascular density, were determined by immunohistochemistry. Levels of vascular endothelium growth factor (VEGF) and prostaglandin E2 (PGE2) were determined by ELISA, and levels of nitric oxide (NO) by Griess reaction. PAF-R expression was analysed by immunohistochemistry and flow cytometry.

Results
Inoculation of apoptotic cells before EAT implantation stimulated tumour growth. This effect was reversed by in vivo pre-treatment with WEB2170. This treatment also reduced tumour growth and modified the microenvironment by reducing PGE2, VEGF and NO production. In B16F10 melanoma, WEB2170 alone or in association with DTIC significantly reduced tumour volume. Survival of the tumour-bearing mice was not affected by WEB2170 treatment but was significantly improved by the combination of DTIC with WEB2170. Tumour microenvironment elements were among the targets of the combination therapy since the relative frequency of COX-2 and galectin-3 positive cells and the microvascular density within the tumour mass were significantly reduced by treatment with WEB2170 or DTIC alone or in combination. Antibodies to PAF-R stained the cells from inside the tumour, but not the tumour cells grown in vitro. At the tissue level, a few cells (probably macrophages) stained positively with antibodies to PAF-R.

Conclusions
We suggest that PAF-R-dependent pathways are activated during experimental tumour growth, modifying the microenvironment and the phenotype of the tumour macrophages in such a way as to favour tumour growth. Combination therapy with a PAF-R antagonist and a chemotherapeutic drug may represent a new and promising strategy for the treatment of some tumours.
Microporation is a valuable transfection method for efficient gene delivery into human umbilical cord blood-derived mesenchymal stem cells
Authors: Lim Jung Yeon , Park Sun Hwa , Jeong Chang Hyun , Oh Ji Hyeon , Kim Seong Muk , Ryu Chung Hun , Park Soon A , Ahn Jae Geun , Oh Wonil , Jeun Sin-Soo , Chang Jong Wook 
Published: May 2010

Abstract

Background
Mesenchymal stem cells (MSCs) are an attractive source of adult stem cells for therapeutic application in clinical study. Genetic modification of MSCs with beneficial genes makes them more effective for therapeutic use. However, it is difficult to transduce genes into MSCs by common transfection methods, especially nonviral methods. In this study, we applied microporation technology as a novel electroporation technique to introduce enhanced green fluorescent protein (EGFP) and brain-derived neurotropfic factor (BDNF) plasmid DNA into human umbilical cord blood-derived MSCs (hUCB-MSCs) with significant efficiency, and investigated the stem cell potentiality of engineered MSCs through their phenotypes, proliferative capacity, ability to differentiate into multiple lineages, and migration ability towards malignant glioma cells.

Results
Using microporation with EGFP as a reporter gene, hUCB-MSCs were transfected with higher efficiency (83%) and only minimal cell damage than when conventional liposome-based reagent (<20%) or established electroporation methods were used (30-40%). More importantly, microporation did not affect the immunophenotype of hUCB-MSCs, their proliferation activity, ability to differentiate into mesodermal and ectodermal lineages, or migration ability towards cancer cells. In addition, the BDNF gene could be successfully transfected into hUCB-MSCs, and BDNF expression remained fairly constant for the first 2 weeks in vitro and in vivo. Moreover, microporation of BDNF gene into hUCB-MSCs promoted their in vitro differentiation into neural cells.

Conclusion
Taken together, the present data demonstrates the value of microporation as an efficient means of transfection of MSCs without changing their multiple properties. Gene delivery by microporation may enhance the feasibility of transgenic stem cell therapy.
Comparative study of the antioxidant and reactive oxygen species scavenging properties in the extracts of the fruits of Terminalia chebula, Terminalia belerica and Emblica officinalis
Authors: Hazra Bibhabasu , Sarkar Rhitajit , Biswas Santanu , Mandal Nripendranath 
Published: May 2010

AbstractBackgroundCellular damage caused by reactive oxygen species (ROS) has been implicated in several diseases, and hence natural antioxidants have significant importance in human health. The present study was carried out to evaluate thein vitroantioxidant and reactive oxygen species scavenging activities ofTerminalia chebula,Terminalia belericaandEmblica officinalisfruit extracts.MethodsThe 70% methanol extracts were studied forin vitrototal antioxidant activity along with phenolic and flavonoid contents and reducing power. Scavenging ability of the extracts for radicals like DPPH, hydroxyl, superoxide, nitric oxide, hydrogen peroxide, peroxynitrite, singlet oxygen, hypochlorous acid were also performed to determine the potential of the extracts.ResultsThe ability of the extracts of the fruits in exhibiting their antioxative properties follow the orderT. chebula>E. officinalis>T. belerica. The same order is followed in their flavonoid content, whereas in case of phenolic content it becomesE. officinalis>T. belerica>T. chebula. In the studies of free radicals' scavenging, where the activities of the plant extracts were inversely proportional to their IC50values,T. chebulaandE. officinaliswere found to be taking leading role with the orders ofT. chebula>E. officinalis>T. belericafor superoxide and nitric oxide, andE. officinalis>T. belerica>T. chebulafor DPPH and peroxynitrite radicals. Miscellaneous results were observed in the scavenging of other radicals by the plant extracts, viz.,T. chebula>T. belerica>E. officinalisfor hydroxyl,T. belerica>T. chebula>E. officinalisfor singlet oxygen andT. belerica>E. officinalis>T. chebulafor hypochlorous acid. In a whole, the studied fruit extracts showed quite good efficacy in their antioxidant and radical scavenging abilities, compared to the standards.ConclusionsThe evidences as can be concluded from the study of the 70% methanol extract of the fruits ofTerminalia chebula,Terminalia belericaandEmblica officinalis, imposes the fact that they might be useful as potent sources of natural antioxidant.
Recruitment of multiple stakeholders to health services research: Lessons from the front lines
Authors: Kho Michelle E , Rawski Ellen , Makarski Julie , Brouwers Melissa C 
Published: May 2010

AbstractBackgroundSelf-administered surveys are an essential methodological tool for health services and knowledge translation research, and engaging end-users of the research is critical. However, few documented accounts of the efforts invested in recruitment of multiple different stakeholders to one health services research study exist. Here, we highlight the challenges of recruiting key stakeholders (policy-makers, clinicians, guideline developers) to a Canadian Institutes of Health Research (CIHR) funded health services research (HSR) study aimed to develop an updated and refined version of a guideline appraisal tool, the AGREE.MethodsUsing evidence-based methods of recruitment, our goal was to recruit 192 individuals: 80 international guideline developers, 80 Canadian clinicians and 32 Canadian policy/decision-makers. We calculated the participation rate and the recruitment efficiency.ResultsWe mailed 873 invitation letters. Of 838 approached, our participation rate was 29%(240) and recruitment efficiency, 19%(156). One policy-maker manager did not allow policy staff to participate in the study.ConclusionsBased on the results from this study, we suggest that future studies aiming to engage similar stakeholders in HSR over sample by at least 5 times to achieve their target sample size and allow for participant withdrawals. We need continued efforts to communicate the value of research between researchers and end-users of research (policy-makers, clinicians, and other researchers), integration of participatory research strategies, and promotion of the value of end-user involvement in research. Future research to understand methods of improving recruitment efficiency and engaging key stakeholders in HSR is warranted.
Towards malaria risk prediction in Afghanistan using remote sensing
Authors: Adimi Farida , Soebiyanto Radina P , Safi Najibullah , Kiang Richard 
Published: May 2010

Abstract

Background
Malaria is a significant public health concern in Afghanistan. Currently, approximately 60% of the population, or nearly 14 million people, live in a malaria-endemic area. Afghanistan's diverse landscape and terrain contributes to the heterogeneous malaria prevalence across the country. Understanding the role of environmental variables on malaria transmission can further the effort for malaria control programme.

Methods
Provincial malaria epidemiological data (2004-2007) collected by the health posts in 23 provinces were used in conjunction with space-borne observations from NASA satellites. Specifically, the environmental variables, including precipitation, temperature and vegetation index measured by the Tropical Rainfall Measuring Mission and the Moderate Resolution Imaging Spectoradiometer, were used. Regression techniques were employed to model malaria cases as a function of environmental predictors. The resulting model was used for predicting malaria risks in Afghanistan. The entire time series except the last 6 months is used for training, and the last 6-month data is used for prediction and validation.

Results
Vegetation index, in general, is the strongest predictor, reflecting the fact that irrigation is the main factor that promotes malaria transmission in Afghanistan. Surface temperature is the second strongest predictor. Precipitation is not shown as a significant predictor, as it may not directly lead to higher larval population. Autoregressiveness of the malaria epidemiological data is apparent from the analysis. The malaria time series are modelled well, with provincial average R2 of 0.845. Although the R2 for prediction has larger variation, the total 6-month cases prediction is only 8.9% higher than the actual cases.

Conclusions
The provincial monthly malaria cases can be modelled and predicted using satellite-measured environmental parameters with reasonable accuracy. The Third Strategic Approach of the WHO EMRO Malaria Control and Elimination Plan is aimed to develop a cost-effective surveillance system that includes forecasting, early warning and detection. The predictive and early warning capabilities shown in this paper support this strategy.
Psychological Factors in Asthma
Authors: Van Lieshout Ryan J , MacQueen Glenda 
Published: May 2010

AbstractAsthma has long been considered a condition in which psychological factors have a role. As in many illnesses, psychological variables may affect outcome in asthma via their effects on treatment adherence and symptom reporting. Emerging evidence suggests that the relation between asthma and psychological factors may be more complex than that, however. Central cognitive processes may influence not only the interpretation of asthma symptoms but also the manifestation of measurable changes in immune and physiologic markers of asthma. Furthermore, asthma and major depressive disorder share several risk factors and have similar patterns of dysregulation in key biologic systems, including the neuroendocrine stress response, cytokines, and neuropeptides. Despite the evidence that depression is common in people with asthma and exerts a negative impact on outcome, few treatment studies have examined whether improving symptoms of depression do, in fact, result in better control of asthma symptoms or improved quality of life in patients with asthma.
Distribution of hepatitis C virus genotypes among injecting drug users in Lebanon
Authors: Mahfoud Ziyad , Kassak Kassem , Kreidieh Khalil , Shamra Sarah , Ramia Sami 
Published: May 2010

Abstract

Background
The aim of this study is to determine the prevalence of anti-HCV among injecting drug users (IDUs) in Lebanon, to establish the current prevalence of HCV genotypes in this population and to determine whether demographic characteristics and behavioral variables differ between participants who were HCV-RNA positive and those who were HCV-RNA negative or between the different genotypes. Participants were recruited using respondent-driven sampling method. The blood samples were collected as dried blood spots and then eluted to be tested for HCV, HBV and HIV by ELISA. Anti-HCV positive samples were subjected to RNA extraction followed by qualitative detection and genotyping.

Results
Among 106 IDUs, 56 (52.8%) were anti-HCV-positive. The two groups did not differ in terms of age, marital status, and nationality. As for the behavioral variable, there was a trend of increased risky behaviors among the HCV-RNA positive group as compared to the HCV-RNA negative group but none of the variables reached statistical significance. Half (50%) of the 56 anti-HCV-positive were HCV-RNA positive. Genotype 3 was the predominant one (57.1%) followed by genotype 1 (21%) and genotype 4 (18%).

Conclusions
The predominance of genotype 3 seems to be the predominant genotype among IDUs in Lebanon, a situation similar to that among IDUs in Western Europe. This study provides a base-line against possible future radical epidemiological variant that might occur in IDUs.
Metabolic effects of influenza virus infection in cultured animal cells: Intra- and extracellular metabolite profiling
Authors: Ritter Joachim B , Wahl Aljoscha S , Freund Susann , Genzel Yvonne , Reichl Udo 
Published: May 2010

Abstract

Background
Many details in cell culture-derived influenza vaccine production are still poorly understood and approaches for process optimization mainly remain empirical. More insights on mammalian cell metabolism after a viral infection could give hints on limitations and cell-specific virus production capacities. A detailed metabolic characterization of an influenza infected adherent cell line (MDCK) was carried out based on extracellular and intracellular measurements of metabolite concentrations.

Results
For most metabolites the comparison of infected (human influenza A/PR/8/34) and mock-infected cells showed a very similar behavior during the first 10-12 h post infection (pi). Significant changes were observed after about 12 h pi: (1) uptake of extracellular glucose and lactate release into the cell culture supernatant were clearly increased in infected cells compared to mock-infected cells. At the same time (12 h pi) intracellular metabolite concentrations of the upper part of glycolysis were significantly increased. On the contrary, nucleoside triphosphate concentrations of infected cells dropped clearly after 12 h pi. This behaviour was observed for two different human influenza A/PR/8/34 strains at slightly different time points.

Conclusions
Comparing these results with literature values for the time course of infection with same influenza strains, underline the hypothesis that influenza infection only represents a minor additional burden for host cell metabolism. The metabolic changes observed after12 h pi are most probably caused by the onset of apoptosis in infected cells. The comparison of experimental data from two variants of the A/PR/8/34 virus strain (RKI versus NIBSC) with different productivities and infection dynamics showed comparable metabolic patterns but a clearly different timely behavior. Thus, infection dynamics are obviously reflected in host cell metabolism.
Correlation Network Analysis reveals a sequential reorganization of metabolic and transcriptional states during germination and gene-metabolite relationships in developing seedlings of Arabidopsis
Authors: Allen Elizabeth , Moing Annick , Ebbels Timothy MD , Maucourt Mickaël , Tomos A Deri , Rolin Dominique , Hooks Mark A 
Published: May 2010

AbstractBackgroundHolistic profiling and systems biology studies of nutrient availability are providing more and more insight into the mechanisms by which gene expression responds to diverse nutrients and metabolites. Less is known about the mechanisms by which gene expression is affected by endogenous metabolites, which can change dramatically during development. Multivariate statistics and correlation network analysis approaches were applied to non-targeted profiling data to investigate transcriptional and metabolic states and to identify metabolites potentially influencing gene expression during the heterotrophic to autotrophic transition of seedling establishment.ResultsMicroarray-based transcript profiles were obtained from extracts of Arabidopsis seeds or seedlings harvested from imbibition to eight days-old.1H-NMR metabolite profiles were obtained for corresponding samples. Analysis of transcript data revealed high differential gene expression through seedling emergence followed by a period of less change. Differential gene expression increased gradually to day 8, and showed two days, 5 and 7, with a very high proportion of up-regulated genes, including transcription factor/signaling genes. Network cartography using spring embedding revealed two primary clusters of highly correlated metabolites, which appear to reflect temporally distinct metabolic states. Principle Component Analyses of both sets of profiling data produced a chronological spread of time points, which would be expected of a developmental series. The network cartography of the transcript data produced two distinct clusters comprising days 0 to 2 and days 3 to 8, whereas the corresponding analysis of metabolite data revealed a shift of day 2 into the day 3 to 8 group. A metabolite and transcript pair-wise correlation analysis encompassing all time points gave a set of 237 highly significant correlations. Of 129 genes correlated to sucrose, 44 of them were known to be sucrose responsive including a number of transcription factors.ConclusionsMicroarray analysis during germination and establishment revealed major transitions in transcriptional activity at time points potentially associated with developmental transitions. Network cartography using spring-embedding indicate that a shift in the state of nutritionally important metabolites precedes a major shift in the transcriptional state going from germination to seedling emergence. Pair-wise linear correlations of transcript and metabolite levels identified many genes known to be influenced by metabolites, and provided other targets to investigate metabolite regulation of gene expression during seedling establishment.