bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide landscape of liver X receptor chromatin binding and gene regulation in human macrophages
Authors: Pehkonen Petri , Welter-Stahl Lynn , Diwo Janine , Ryynänen Jussi , Wienecke-Baldacchino Anke , Heikkinen Sami , Treuter Eckardt , Steffensen Knut R , Carlberg Carsten 
Published: January 2012

AbstractBackgroundThe liver X receptors (LXRs) are oxysterol sensing nuclear receptors with multiple effects on metabolism and immune cells. However, the complete genome-wide cistrome of LXR in cells of human origin has not yet been provided.ResultsWe performed ChIP-seq in phorbol myristate acetate-differentiated THP-1 cells (macrophage-type) after stimulation with the potent synthetic LXR ligand T0901317 (T09). Microarray gene expression analysis was performed in the same cellular model. We identified 1357 genome-wide LXR locations (FDR < 1%), of which 526 were observed after T09 treatment.De novoanalysis of LXR binding sequences identified a DR4-type element as the major motif. On mRNA level T09 up-regulated 1258 genes and repressed 455 genes. Our results show that LXR actions are focused on 112 genomic regions that contain up to 11 T09 target genes per region under the control of highly stringent LXR binding sites with individual constellations for each region. We could confirm that LXR controls lipid metabolism and transport and observed a strong association with apoptosis-related functions.ConclusionsThis first report on genome-wide binding of LXR in a human cell line provides new insights into the transcriptional network of LXR and its target genes with their link to physiological processes, such as apoptosis.The gene expression microarray and sequence data have been submitted collectively to the NCBI Gene Expression Omnibushttp://www.ncbi.nlm.nih.gov/geounder accession number GSE28319.
Adoptive transfer of IL-4Rα+ macrophages is sufficient to enhance eosinophilic inflammation in a mouse model of allergic lung inflammation
Authors: Ford Andrew Q , Dasgupta Preeta , Mikhailenko Irina , Smith Elizabeth MP , Noben-Trauth Nancy , Keegan Achsah D 
Published: January 2012

AbstractBackgroundThe IL-4 receptor α (IL-4Rα) chain has a broad expression pattern and participates in IL-4 and IL-13 signaling, allowing it to influence several pathological components of allergic lung inflammation. We previously reported that IL-4Rα expression on both bone marrow-derived and non-bone marrow-derived cells contributed to the severity of allergic lung inflammation. There was a correlation between the number of macrophages expressing the IL-4Rα, CD11b, and IAd, and the degree of eosinophilia in ovalbumin challenged mice. The engagement of the IL-4Rα by IL-4 or IL-13 is able to stimulate the alternative activation of macrophages (AAM). The presence of AAM has been correlated with inflammatory responses to parasites and allergens. Therefore, we hypothesized that IL-4Rα+AAM play an active role in allergic lung inflammation. To directly determine the role of AAM in allergic lung inflammation, M-CSF-dependent macrophages (BMM) were prepared from the bone-marrow of IL-4Rα positive and negative mice and transferred to IL-4RαxRAG2-/-mice. Wild type TH2 cells were provided exogenously.ResultsMice receiving IL-4Rα+/+BMM showed a marked increase in the recruitment of eosinophils to the lung after challenge with ovalbumin as compared to mice receiving IL-4Rα-/-BMM. As expected, the eosinophilic inflammation was dependent on the presence of TH2 cells. Furthermore, we observed an increase in cells expressing F4/80 and Mac3, and the AAM marker YM1/2 in the lungs of mice receiving IL-4Rα+/+BMM. The BAL fluid from these mice contained elevated levels of eotaxin-1, RANTES, and CCL2.ConclusionsThese results demonstrate that transfer of IL-4Rα + macrophages issufficientto enhance TH2-driven, allergic inflammation. They further show that stimulation of macrophages through IL-4Rα leads to their alternative activation andpositive contributionto the TH2-driven allergic inflammatory response in the lung. Since an increase in AAM and their products has been observed in patients with asthma exacerbations, these results suggest that AAM may be targeted to alleviate exacerbations.
Transcriptional activation of microRNA-34a by NF-kappa B in human esophageal cancer cells
Authors: Li Juan , Wang Kai , Chen Xuedan , Meng Hui , Song Min , Wang Yan , Xu Xueqing , Bai Yun 
Published: January 2012

Abstract

Background
miR-34a functions as an important tumor suppressor during the process of carcinogenesis. However, the mechanism of miR-34a dysregulation in human malignancies has not been well elucidated. Our study aimed to further investigate the regulation mechanism of miR-34a.

Results
We found that overexpression of NF-kappa B p65 subunit could increase miR-34a levels in EC109, an esophageal squamous cancer cell line, while ectopic expression of DN IkappaB leaded to a significant reduction of miR-34a expression. Bioinformatics analysis suggested three putative KB sites in promoter region of miR-34a gene. Mutation two of these KB sites impaired p65 induced miR-34a transcriptional activity. Chromatin immunoprecipitation and electrophoretic mobility shift assays both showed that NF-kappaB could specifically bind to the third KB site located in miR-34a promoter. In addition, we found that overexpression of NF-kappaB p65 could not successfully induce miR-34a expression in esophageal cancer cell lines with mutant p53 or decreased p53. Reporter assay further showed that NF-kappaB-induced miR-34a transcriptional activity was reduced by p53 impairment. Nevertheless, CHIP analysis suggested binding of NF-kappaB to miR-34a promoter was not affected in cells with mutant p53.

Conclusions
Our work indicates a novel mechanism of miR-34a regulation that NF-kappaB could elevate miR-34a expression levels through directly binding to its promoter. And wildtype p53 is responsible for NF-kappaB-mediated miR-34a transcriptional activity but not for NF-kappaB binding. These findings might be helpful in understanding miR-34a abnormality in human malignancies and open new perspectives for the roles of miR-34a and NF-kappaB in tumor progression.
Long-term effects of treatment and response in patients with chronic hepatitis C on quality of life. An international, multicenter, randomized, controlled study
Authors: Bezemer Geert , Van Gool Arthur R , Verheij-Hart Elke , Hansen Bettina E , Lurie Yoav , Esteban Juan I , Lagging Martin , Negro Francesco , Zeuzem Stefan , Ferrari Carlo , Pawlotsky Jean-Michel , Neumann Avidan U , Schalm Solko W , de Knegt Robert J ,   for the DITTO-HCV Study Group
Published: January 2012

Abstract

Background
Hepatitis C decreases health related quality of life (HRQL) which is further diminished by antiviral therapy. HRQL improves after successful treatment. This trial explores the course of and factors associated with HRQL in patients given individualized or standard treatment based on early treatment response (Ditto-study).

Methods
The Short Form (SF)-36 Health Survey was administered at baseline (n = 192) and 24 weeks after the end of therapy (n = 128).

Results
At baseline HRQL was influenced by age, participating center, severity of liver disease and income. Exploring the course of HRQL (scores at follow up minus baseline), only the dimension general health increased. In this dimension patients with a relapse or sustained response differed from non-responders. Men and women differed in the dimension bodily pain. Treatment schedule did not influence the course of HRQL.

Conclusions
Main determinants of HRQL were severity of liver disease, age, gender, participating center and response to treatment. Our results do not exclude a more profound negative impact of individualized treatment compared to standard, possibly caused by higher doses and extended treatment duration in the individualized group. Antiviral therapy might have a more intense and more prolonged negative impact on females.
Cancer-initiating cells derived from established cervical cell lines exhibit stem-cell markers and increased radioresistance
Authors: López Jacqueline , Poitevin Adela , Mendoza-Martínez Veverly , Pérez-Plasencia Carlos , García-Carrancá Alejandro 
Published: January 2012

Abstract

Background
Cancer-initiating cells (CICs) are proposed to be responsible for the generation of metastasis and resistance to therapy. Accumulating evidences indicates CICs are found among different human cancers and cell lines derived from them. Few studies address the characteristics of CICs in cervical cancer. We identify biological features of CICs from four of the best-know human cell lines from uterine cervix tumors. (HeLa, SiHa, Ca Ski, C-4 I).

Methods
Cells were cultured as spheres under stem-cell conditions. Flow cytometry was used to detect expression of CD34, CD49f and CD133 antigens and Hoechst 33342 staining to identify side population (SP). Magnetic and fluorescence-activated cell sorting was applied to enrich and purify populations used to evaluate tumorigenicity in nude mice. cDNA microarray analysis and in vitro radioresistance assay were carried out under standard conditions.

Results
CICs, enriched as spheroids, were capable to generate reproducible tumor phenotypes in nu-nu mice and serial propagation. Injection of 1 × 103 dissociated spheroid cells induced tumors in the majority of animals, whereas injection of 1 × 105 monolayer cells remained nontumorigenic. Sphere-derived CICs expressed CD49f surface marker. Gene profiling analysis of HeLa and SiHa spheroid cells showed up-regulation of CICs markers characteristic of the female reproductive system. Importantly, epithelial to mesenchymal (EMT) transition-associated markers were found highly expressed in spheroid cells. More importantly, gene expression analysis indicated that genes required for radioresistance were also up-regulated, including components of the double-strand break (DSB) DNA repair machinery and the metabolism of reactive oxygen species (ROS). Dose-dependent radiation assay indicated indeed that CICs-enriched populations exhibit an increased resistance to ionizing radiation (IR).

Conclusions
We characterized a self-renewing subpopulation of CICs found among four well known human cancer-derived cell lines (HeLa, SiHa, Ca Ski and C-4 I) and found that they express characteristic markers of stem cell, EMT and radioresistance. The fact that CICs demonstrated a higher degree of resistance to radiation than differentiated cells suggests that specific detection and targeting of CICs could be highly valuable for the therapy of tumors from the uterine cervix.
Role of extrathyroidal TSHR expression in adipocyte differentiation and its association with obesity
Authors: Lu Sumei , Guan Qingbo , Liu Yuantao , Wang Haibo , Xu Wei , Li Xia , Fu Yuchang , Gao Ling , Zhao Jiajun , Wang Xiangdong 
Published: January 2012

AbstractBackgroundObesity is known to be associated with higher risks of cardiovascular disease, metabolic syndrome, and diabetes mellitus. Thyroid-stimulating hormone (TSHR) is the receptor for thyroid-stimulating hormone (TSH, or thyrotropin), the key regulator of thyroid functions. The expression of TSHR, once considered to be limited to thyrocytes, has been so far detected in many extrathyroidal tissues including liver and fat. Previous studies have shown that TSHR expression is upregulated when preadipocytes differentiate into mature adipocytes, suggestive of a possible role of TSHR in adipogenesis. However, it remains unclear whether TSHR expression in adipocytes is implicated in the pathogenesis of obesity.MethodsIn the present study, TSHR expression in adipose tissues from both mice and human was analyzed, and its association with obesity was evaluated.ResultsWe here showed that TSHR expression was increased at both mRNA and protein levels when 3T3-L1 preadipocytes were induced to differentiate. Knockdown of TSHR blocked the adipocyte differentiation of 3T3-L1 preadipocytes as evaluated by Oil-red-O staining for lipid accumulation and by RT-PCR analyses of PPAR-γ and ALBP mRNA expression. We generated obesity mice (C57/BL6) by high-fat diet feeding and found that the TSHR protein expression in visceral adipose tissues from obesity mice was significantly higher in comparison with the non-obesity control mice (P< 0.05). Finally, the TSHR expression in adipose tissues was determined in 120 patients. The results showed that TSHR expression in subcutaneous adipose tissue is correlated with BMI (body mass index).ConclusionTaken together, these results suggested that TSHR is an important regulator of adipocyte differentiation. Dysregulated expression of TSHR in adipose tissues is associated with obesity, which may involve a mechanism of excess adipogenesis.
Evaluation of health related quality of life in irritable bowel syndrome patients
Authors: Jamali Raika , Jamali Arsia , Poorrahnama Maryam , Omidi Abdollah , Jamali Bardia , Moslemi Neda , Ansari Reza , Dolatshahi Shahab , Ebrahimi Daryani Naser 
Published: January 2012

Abstract

Background
Quality of life (QOL) is an important measure in the management of Irritable Bowel Syndrome (IBS). Controversy exists in the findings of studies evaluating QOL in IBS subtypes, and little is known about this issue in Iranian patients. Determination of the factors affecting QOL in IBS patients may influence treatment outcomes. The aims of this study are to: 1) compare QOL between subtypes in a sample of Iranian IBS patients, 2) determine the factors associated with QOL in IBS.

Methods
This cross sectional study included two hundred and fifty IBS patients with the mean age (± standard deviation) of 31.62 (± 11.93) years that were referred to outpatient gastroenterology clinic. IBS patients were diagnosed based on Rome-3 criteria by a gastroenterologist, and then they were categorized into three subtypes according to the predominant type of bowel habit. The "QOL specific for IBS", "Stait-trait anxiety inventory", and "Beck depression inventory-2" questioners were used to evaluate QOL, anxiety, and depression symptoms, respectively.

Results
The mean QOL scores in IBS mixed subtype (71.7 ± 25.57), constipation predominant subtype (80.28 ± 25.57), and diarrhea predominant subtype (76.43 ± 19.13) were not different. (P value: 0.05) In multivariate linear regression analysis, anxiety symptom scores were inversely correlated with QOL scores. [Standardized beta: -0.43, (95% confidence interval: -0.70, -0.39), P value: < 0.01]

Conclusion
It seems reasonable to manage anxiety symptoms properly in IBS patients since this might increase their QOL.
Involvement of Plasmodium falciparum protein kinase CK2 in the chromatin assembly pathway
Authors: Dastidar Eeshita G , Dayer Guillem , Holland Zoe M , Dorin-Semblat Dominique , Claes Aurélie , Chêne Arnaud , Sharma Amit , Hamelin Romain , Moniatte Marc , Lopez-Rubio Jose-Juan , Scherf Artur , Doerig Christian 
Published: January 2012

Abstract

Background
Protein kinase CK2 is a pleiotropic serine/threonine protein kinase with hundreds of reported substrates, and plays an important role in a number of cellular processes. The cellular functions of Plasmodium falciparum CK2 (PfCK2) are unknown. The parasite's genome encodes one catalytic subunit, PfCK2α, which we have previously shown to be essential for completion of the asexual erythrocytic cycle, and two putative regulatory subunits, PfCK2β1 and PfCK2β2.

Results
We now show that the genes encoding both regulatory PfCK2 subunits (PfCK2β1 and PfCK2β2) cannot be disrupted. Using immunofluorescence and electron microscopy, we examined the intra-erythrocytic stages of transgenic parasite lines expressing hemagglutinin (HA)-tagged catalytic and regulatory subunits (HA-CK2α, HA-PfCK2β1 or HA-PfCK2β2), and localized all three subunits to both cytoplasmic and nuclear compartments of the parasite. The same transgenic parasite lines were used to purify PfCK2β1- and PfCK2β2-containing complexes, which were analyzed by mass spectrometry. The recovered proteins were unevenly distributed between various pathways, with a large proportion of components of the chromatin assembly pathway being present in both PfCK2β1 and PfCK2β2 precipitates, implicating PfCK2 in chromatin dynamics. We also found that chromatin-related substrates such as nucleosome assembly proteins (Naps), histones, and two members of the Alba family are phosphorylated by PfCK2α in vitro.

Conclusions
Our reverse-genetics data show that each of the two regulatory PfCK2 subunits is required for completion of the asexual erythrocytic cycle. Our interactome study points to an implication of PfCK2 in many cellular pathways, with chromatin dynamics being identified as a major process regulated by PfCK2. This study paves the way for a kinome-wide interactomics-based approach to elucidate protein kinase function in malaria parasites.
Traditional use of medicinal plants in the boreal forest of Canada: review and perspectives
Authors: Uprety Yadav , Asselin Hugo , Dhakal Archana , Julien Nancy 
Published: January 2012

Abstract

Background
The boreal forest of Canada is home to several hundred thousands Aboriginal people who have been using medicinal plants in traditional health care systems for thousands of years. This knowledge, transmitted by oral tradition from generation to generation, has been eroding in recent decades due to rapid cultural change. Until now, published reviews about traditional uses of medicinal plants in boreal Canada have focused either on particular Aboriginal groups or on restricted regions. Here, we present a review of traditional uses of medicinal plants by the Aboriginal people of the entire Canadian boreal forest in order to provide comprehensive documentation, identify research gaps, and suggest perspectives for future research.

Methods
A review of the literature published in scientific journals, books, theses and reports.

Results
A total of 546 medicinal plant taxa used by the Aboriginal people of the Canadian boreal forest were reported in the reviewed literature. These plants were used to treat 28 disease and disorder categories, with the highest number of species being used for gastro-intestinal disorders, followed by musculoskeletal disorders. Herbs were the primary source of medicinal plants, followed by shrubs. The medicinal knowledge of Aboriginal peoples of the western Canadian boreal forest has been given considerably less attention by researchers. Canada is lacking comprehensive policy on harvesting, conservation and use of medicinal plants. This could be explained by the illusion of an infinite boreal forest, or by the fact that many boreal medicinal plant species are widely distributed.

Conclusion
To our knowledge, this review is the most comprehensive to date to reveal the rich traditional medicinal knowledge of Aboriginal peoples of the Canadian boreal forest. Future ethnobotanical research endeavours should focus on documenting the knowledge held by Aboriginal groups that have so far received less attention, particularly those of the western boreal forest. In addition, several critical issues need to be addressed regarding the legal, ethical and cultural aspects of the conservation of medicinal plant species and the protection of the associated traditional knowledge.
A simple and efficient method for the long-term preservation of plant cell suspension cultures
Authors: Boisson Anne-Marie , Gout Elisabeth , Bligny Richard , Rivasseau Corinne 
Published: January 2012

Abstract

Background
The repeated weekly subculture of plant cell suspension is labour intensive and increases the risk of variation from parental cells lines. Most of the procedures to preserve cultures are based on controlled freezing/thawing and storage in liquid nitrogen. However, cells viability after unfreezing is uncertain. The long-term storage and regeneration of plant cell cultures remains a priority.

Results
Sycamore (Acer pseudoplatanus) and Arabidopsis cell were preserved over six months as suspensions cultures in a phosphate-free nutrient medium at 5°C. The cell recovery monitored via gas exchange measurements and metabolic profiling using in vitro and in vivo
13C- and 31P-NMR took a couple of hours, and cell growth restarted without appreciable delay. No measurable cell death was observed.

Conclusion
We provide a simple method to preserve physiologically homogenous plant cell cultures without subculture over several months. The protocol based on the blockage of cell growth and low culture temperature is robust for heterotrophic and semi-autotrophic cells and should be adjustable to cell lines other than those utilised in this study. It requires no specialized equipment and is suitable for routine laboratory use.
Skin toxicity from external beam radiation therapy in breast cancer patients: protective effects of Resveratrol, Lycopene, Vitamin C and anthocianin (Ixor®)
Authors: Franco Rossella Di , Calvanese MariaGrazia , Murino Paola , Manzo Roberto , Guida Cesare , Gennaro Davide Di , Anania Caterina , Ravo Vincenzo 
Published: January 2012

Abstract

Introduction
This is an observational study and the aim is to evaluate the effect of dietary supplements based on Resveratrol, Lycopene, Vitamin C and Anthocyanins (Ixor®) in reducing skin toxicity due to external beam radiotherapy in patients affected by breast cancer.

Materials and methods
71 patients were enrolled and they were divided in two different groups: a control group (CG) of 41 patients treated with prophylactic topical therapy based on hyaluronic acid and topical steroid therapy in case of occurrence of radiodermatitis, and a Ixor-Group (IG) of 30 patients treated also with an oral therapy based on Resveratrol, Lycopene, Vitamin C and Anthocyanin (Ixor®) at a dose of 2 tablets/day, starting from 10 days before the radiation treatment until 10 days after the end of treatment. Skin toxicity has been related to PTV, to breast volume that received a radiation dose equal or lower than 107%, included between 107% and 110%, or greater than 110% of the prescribed dose. Moreover it's been studied the relationship between skin toxicity and the chemotherapy schedule used before treatment. We calculated in both groups the percentage of patients who had a skin toxicity of grade 2 or 3 (according to RTOG scale). Absolute risk reduction (ARR), relative risk (RR) and odds ratio (OR) have been calculated for each relationship.

Results
Control Group (CG) patients with a PTV > 500 ml presented skin toxicity G2 + G3 in 30% of cases, versus 25% of Ixor-Group (IG) [OR 0.77]. In patients with a PTV < 500 ml G2 + G3 toxicity was 0% in the IG compared to 18% in CG (OR 0.23). When Dmax was less than or equal to 107% of the prescribed dose skin toxicity was G2 + G3 in 12.5% in CG, versus 0% in IG (OR 0.73), instead when Dmax was included between 107 and 110% of the prescribed dose, G2 + G3 skin toxicity was 35% in CG and 21% in IG (OR 0.50). In patients undergoing chemotherapy with anthracyclines and taxanes, G2 + G3 toxicity was 27% in CG, against 20% in IG (OR 0.68).

Conclusions
The protective effect of Resveratrol, Lycopene, Vitamin C and Anthocyanin (Ixor®) is more detected in patients with PTV < 500 ml, when Dmax reaches values lower or equal to 107%, but not exceeding 110% of the prescribed dose, and in patients undergoing adjuvant chemotherapy with anthracyclines and taxanes.