bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hepatoprotective activities of a sesquiterpene-rich fraction from the aerial part of Cichorium glandulosum
Authors: Yang Wei-Jun , Luo Yu-Qin , Aisa Haji Akber , Xin Xue-Lei , Totahon Z , Mao Yan , Hu Meng-Ying , Xu Lei , Zhang Rui-Ping 
Published: October 2012

Abstract

Background

Cichorium glandulosum Boiss. et Huet is used for treatment of liver disorders, and its effects are attributed to sesquiterpenes. This study aims to investigate the hepatoprotective effects of a sesquiterpene-rich fraction (SRF) from the aerial part of C. glandulosum on carbon tetrachloride (CCl4)-induced acute hepatotoxicity in mice, and on priming with Bacillus Calmette–Guerin (BCG) followed by lipopolysaccharide (LPS)-induced immunological liver injury in mice.

Methods
SRF was suspended in water and administered to mice at 0.05, 0.10 and 0.20 g/kg body weight for 7 consecutive days. An active control drug (bifendate pills) was suspended in distilled water and administered to mice at 0.40 g/kg body weight for 7 consecutive days. Hepatotoxicity was induced by intraperitoneal injection of 0.1% CCl4 (0.2 mL/mouse) at 13 h before the last drug administration, or by tail intravenous injection of BCG (0.2 mL/mouse) before the first drug administration and LPS (0.2 mL/mouse; 8 μg) at 15 h before the last drug administration. Blood samples and the livers were collected for evaluation of the biochemical parameters of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and total bilirubin (TBIL).

Results
SRF significantly reduced the impact of CCl4 toxicity. The highest dose of SRF (0.20 g/kg) was the most effective, reflected by significant reductions in the levels of AST (P = 0.001), ALT (P = 0.000) and TBIL (P = 0.009). The serum enzymatic levels induced by BCG and subsequent LPS injection were significantly and dose-dependently restored by SRF, reflected by significant reductions in the levels of AST (P = 0.003), ALT (P = 0.003) and TBIL (P = 0.007) for the highest dose of SRF (0.20 g/kg).

Conclusion
SRF is hepatoprotective in animal models of chemical and immunological acute liver injury.
Chromosome anomalies in bone marrow as primary cause of aplastic or hypoplastic conditions and peripheral cytopenia: disorders due to secondary impairment of RUNX1 and MPL genes
Authors: Marletta Cristina , Valli Roberto , Pressato Barbara , Mare Lydia , Montalbano Giuseppe , Menna Giuseppe , Loffredo Giuseppe , Bernardo Maria Ester , Vinti Luciana , Ferrari Simona , Di Cesare-Merlone Alessandra , Zecca Marco , Lo Curto Francesco , Locatelli Franco , Pasquali Francesco , Maserati Emanuela 
Published: October 2012

Abstract

Background
Chromosome changes in the bone marrow (BM) of patients with persistent cytopenia are often considered diagnostic for a myelodysplastic syndrome (MDS). Comprehensive cytogenetic evaluations may give evidence of the real pathogenetic role of these changes in cases with cytopenia without morphological signs of MDS.

Results
Chromosome anomalies were found in the BM of three patients, without any morphological evidence of MDS: 1) an acquired complex rearrangement of chromosome 21 in a boy with severe aplastic anaemia (SAA); the rearrangement caused the loss of exons 2–8 of the RUNX1 gene with subsequent hypoexpression. 2) a constitutional complex rearrangement of chromosome 21 in a girl with congenital thrombocytopenia; the rearrangement led to RUNX1 disruption and hypoexpression. 3) an acquired paracentric inversion of chromosome 1, in which two regions at the breakpoints were shown to be lost, in a boy with aplastic anaemia; the MPL gene, localized in chromosome 1 short arms was not mutated neither disrupted, but its expression was severely reduced: we postulate that the aplastic anaemia was due to position effects acting both in cis and in trans, and causing Congenital Amegakaryocytic Thrombocytopenia (CAMT).

Conclusions
A clonal anomaly in BM does not imply per se a diagnosis of MDS: a subgroup of BM hypoplastic disorders is directly due to chromosome structural anomalies with effects on specific genes, as was the case of RUNX1 and MPL in the patients here reported with diagnosis of SAA, thrombocytopenia, and CAMT. The anomaly may be either acquired or constitutional, and it may act by deletion/disruption of the gene, or by position effects. Full cytogenetic investigations, including a-CGH, should always be part of the diagnostic evaluation of patients with BM aplasia/hypoplasia and peripheral cytopenias.
Vitamin and antioxidant rich diet increases MLH1 promoter DNA methylation in DMT2 subjects
Authors: Switzeny Olivier J , Müllner Elisabeth , Wagner Karl-Heinz , Brath Helmut , Aumüller Eva , Haslberger Alexander G 
Published: October 2012

Abstract

Background
Oxidative stress may lead to an increased level of unrepaired cellular DNA damage, which is discussed as one risk for tumor initiation. Mismatch repair (MMR) enzymes act as proofreading complexes that maintain the genomic integrity and MMR-deficient cells show an increased mutation rate. One important gene in the MMR complex is the MutL homolog 1 (MLH1) gene. Since a diet rich in antioxidants has the potential to counteract harmful effects by reactive oxygen species (ROS), we investigated the impact of an antioxidant, folate, and vitamin rich diet on the epigenetic pattern of MLH1. These effects were analyzed in individuals with non-insulin depended diabetes mellitus type 2 (NIDDM2) and impaired fasting glucose (IFG).

Methods
In this post-hoc analysis of a randomized trial we analyzed DNA methylation of MLH1, MSH2, and MGMT at baseline and after 8 weeks of intervention, consisting of 300 g vegetables and 25 ml plant oil rich in polyunsaturated fatty acids per day. DNA methylation was quantified using combined bisulfite restriction enzyme analysis (COBRA) and pyrosequencing. MLH1 and DNMT1 mRNA expression were investigated by qRT-PCR. DNA damage was assessed by COMET assay. Student’s two-tailed paired t test and one-way ANOVA with Scheffé corrected Post hoc test was used to determine significant methylation and expression differences. Two-tailed Pearson test was used to determine correlations between methylation level, gene expression, and DNA strand break amount.

Results
The intervention resulted in significantly higher CpG methylation in two particular MLH1 promoter regions and the MGMT promoter. DNA strand breaks and methylation levels correlated significantly. The expression of MLH1, DNMT1, and the promoter methylation of MSH2 remained stable. CpG methylation levels and gene expression did not correlate.

Conclusion
This vitamin and antioxidant rich diet affected the CpG methylation of MLH1. The higher methylation might be a result of the ROS scavenging antioxidant rich diet, leading to lower activity of DNA demethylating enzymes. Our results suggest the hypothesis of CpG demethylation via DNA repair enzymes under these circumstances. NIDDM2 and IFG patients benefit from this simple dietary intervention involving epigenetic and DNA repair mechanisms.
Conservation and evolutionary divergence in the activity of receptor-regulated smads
Authors: Sorrentino Gina M , Gillis William Q , Oomen-Hajagos Jamina , Thomsen Gerald H 
Published: October 2012

Abstract

Background
Activity of the Transforming growth factor-β (TGFβ) pathway is essential to the establishment of body axes and tissue differentiation in bilaterians. Orthologs for core pathway members have been found in all metazoans, but uncertain homology of the body axes and tissues patterned by these signals raises questions about the activities of these molecules across the metazoan tree. We focus on the principal canonical transduction proteins (R-Smads) of the TGFβ pathway, which instruct both axial patterning and tissue differentiation in the developing embryo. We compare the activity of R-Smads from a cnidarian (Nematostella vectensis), an arthropod (Drosophila melanogaster), and a vertebrate (Xenopus laevis) in Xenopus embryonic assays.

Results
Overexpressing NvSmad1/5 ventralized Xenopus embryos when expressed in dorsal blastomeres, similar to the effects of Xenopus Smad1. However, NvSmad1/5 was less potent than XSmad1 in its ability to activate downstream target genes in Xenopus animal cap assays. NvSmad2/3 strongly induced general mesendodermal marker genes, but weakly induced ones involved in specifying the Spemann organizer. NvSmad2/3 was unable to induce a secondary trunk axis in Xenopus embryos, whereas the orthologs from Xenopus (XSmad2 and XSmad3) and Drosophila (dSmad2) were capable of doing so. Replacement of the NvSmad2/3 MH2 domain with the Xenopus XSmad2 MH2 slightly increased its inductive capability, but did not confer an ability to generate a secondary body axis.

Conclusions
Vertebrate and cnidarian Smad1/5 have similar axial patterning and induction activities, although NvSmad1/5 is less efficient than the vertebrate gene. We conclude that the activities of Smad1/5 orthologs have been largely conserved across Metazoa. NvSmad2/3 efficiently activates general mesendoderm markers, but is unable to induce vertebrate organizer-specific genes or to produce a secondary body axis in Xenopus. Orthologs dSmad2 and XSmad3 generate a secondary body axis, but activate only low expression of organizer-specific genes that are strongly induced by XSmad2. We suggest that in the vertebrate lineage, Smad2 has evolved a specialized role in the induction of the embryonic organizer. Given the high level of sequence identity between Smad orthologs, this work underscores the functional importance of the emergence and fixation of a few divergent amino acids among orthologs during evolution.
Validation of a multiplex chip-based assay for the detection of autoantibodies against citrullinated peptides
Authors: Hansson Monika , Mathsson Linda , Schlederer Thomas , Israelsson Lena , Matsson Per , Nogueira Leonor , Jakobsson Per-Johan , Lundberg Karin , Malmström Vivianne , Serre Guy , Holmdahl Rikard , Nystrand Mats , Klareskog Lars , Rönnelid Johan 
Published: October 2012

Abstract
Introduction
Autoantibodies directed against citrullinated proteins/peptides (ACPAs) are highly specific and predictive for the development of rheumatoid arthritis (RA). Different subgroups of RA patients, which have different prognoses and may require different treatments, are characterized by different autoantibody profiles. The objective of this study was to develop a microarray for the detection of multiple RA-associated autoantibodies, initially focusing on responses against citrullinated epitopes on candidate autoantigens in RA.

Methods
The microarray is based on Phadia's ImmunoCAP ISAC system, with which reactivity to more than 100 antigens can be analyzed simultaneously, by using minute serum volumes (< 10 μl). Twelve citrullinated peptides, and the corresponding native arginine-containing control peptides, were immobilized in an arrayed fashion onto a chemically modified glass slide, allowing a three-dimensional layer with high binding capacity. The assay was optimized concerning serum dilution and glass surface, whereas each individual antigen was optimized concerning coupling chemistry, antigen concentration, and selection of spotting buffer. The performance of each peptide in the ImmunoCAP ISAC system was compared with the performance in enzyme-linked immunosorbent assays (ELISAs). Serum from 927 RA patients and 461 healthy controls from a matched case-control study were applied onto reaction sites on glass slides, followed by fluorescent-labeled anti-human immunoglobulin G (IgG) antibody. Fluorescence intensities were detected with a laser scanner, and the results analyzed by using image-analysis software.

Results
Strong correlations between the ImmunoCAP ISAC system and ELISA results were found for individual citrullinated peptides (Spearman ρ typically between 0.75 and 0.90). Reactivity of RA sera with the peptides was seen mainly in the anticyclic citrullinated peptide 2 (CCP2)-positive subset, but some additional reactivity with single citrullinated peptides was seen in the anti-CCP2-negative subset. Adjusting for reactivity against arginine-containing control peptides did not uniformly change the diagnostic performance for antibodies against the individual citrullinated peptides.

Conclusions
The multiplexed array, for detection of autoantibodies against multiple citrullinated epitopes on candidate RA autoantigens, will be of benefit in studies of RA pathogenesis, diagnosis, and potentially as a guide to individualized treatment.
Breast vibro-acoustography: initial results show promise
Authors: Alizad Azra , Whaley Dana H , Urban Matthew W , Carter Rickey E , Kinnick Randall R , Greenleaf James F , Fatemi Mostafa 
Published: October 2012

Abstract
Introduction
Vibro-acoustography (VA) is a recently developed imaging modality that is sensitive to the dynamic characteristics of tissue. It detects low-frequency harmonic vibrations in tissue that are induced by the radiation force of ultrasound. Here, we have investigated applications of VA for in vivo breast imaging.

Methods
A recently developed combined mammography-VA system for in vivo breast imaging was tested on female volunteers, aged 25 years or older, with suspected breast lesions on their clinical examination. After mammography, a set of VA scans was acquired by the experimental device. In a masked assessment, VA images were evaluated independently by 3 reviewers who identified mass lesions and calcifications. The diagnostic accuracy of this imaging method was determined by comparing the reviewers' responses with clinical data.

Results
We collected images from 57 participants: 7 were used for training and 48 for evaluation of diagnostic accuracy (images from 2 participants were excluded because of unexpected imaging artifacts). In total, 16 malignant and 32 benign lesions were examined. Specificity for diagnostic accuracy was 94% or higher for all 3 reviewers, but sensitivity varied (69% to 100%). All reviewers were able to detect 97% of masses, but sensitivity for detection of calcification was lower (≤ 72% for all reviewers).

Conclusions
VA can be used to detect various breast abnormalities, including calcifications and benign and malignant masses, with relatively high specificity. VA technology may lead to a new clinical tool for breast imaging applications.
Psychological interventions for difficult-to-treat
depression
Authors: Williams Chris , Ridgway Nicola 
Published: October 2012

SummaryMindfulness-based cognitive therapy (MBCT) may be helpful in preventing
relapse in those with three or more depressive episodes. Recent research
suggests it may also benefit those who have experienced fewer previous
episodes of depression. If confirmed, this raises challenges of how MBCT is
offered, accessed and supported.
Validation of the Security Needs Assessment Profile (SNAP) by a national survey of secure units in England
Authors: Davies Steffan , Collins Mick , Ashwell Chris 
Published: October 2012

Aims and methodThe Security Needs Assessment Profile (SNAP) was developed to provide a detailed description of individual patient's security requirements in the then Trent Region of England. A national survey of secure units was undertaken to examine the content validity of the item structure of SNAP and revise the item definitions to reflect more broadly based clinical practice. A follow-up survey sought views on the usefulness of SNAP in clinical practice.ResultsThirty-five secure units from National Health Service and independent sector providers participated. No new security items were generated. All the item definitions were reviewed, many amended, and a small number revised extensively. Units' security profiles were rated on the original and revised instruments.Clinical implicationsThe revised SNAP has been shown to be generalisable across secure services in England; 92% of respondents agreed or strongly agreed that SNAP would be useful in providing a structured security needs assessment.
Decisions on disclosure to third parties made at MAPP meetings: opinions and practice
Authors: Penny Catherine , Craissati Jackie 
Published: October 2012

Aims and methodWe investigated how decisions regarding disclosure of an offender's history to a third party without the offender's consent are made at Multi-Agency Public Protection (MAPP) meetings. Ten questionnaires were sent to a level 2 MAPP meeting in each of the 33 police and probation areas in London, with a request that the MAPP meeting administrator hand them out to up to 10 regular attendees.ResultsOf 321 questionnaires handed out, 196 were returned, giving a response rate of 61.1%. Seventy-six participants (37%) had made a disclosure without a MAPP meeting discussion in the past 12 months. A total of 109 participants (55.9%) reported that in their experience it had always been possible to reach a consensus on disclosure at MAPP meetings, but participants' responses to five hypothetical scenarios indicated a wide spread of opinions about when a disclosure should be made. Significant proportions of participants endorsed statements suggesting that people have a right to know offenders' histories.Clinical implicationsTraining on the evidence base, law and guidance relevant to disclosure decisions is necessary, and a governance system to monitor and improve decision-making should be considered. Advocacy for offenders may also improve practice.
Nuclear Receptor 5A (NR5A) Family Regulates 5-Aminolevulinic Acid Synthase 1 (ALAS1) Gene Expression in Steroidogenic Cells
Authors: Ju Yunfeng , Mizutani Tetsuya , Imamichi Yoshitaka , Yazawa Takashi , Matsumura Takehiro , Kawabe Shinya , Kanno Masafumi , Umezawa Akihiro , Kangawa Kenji , Miyamoto Kaoru 
Published: October 2012

Abstract5-Aminolevulinic acid synthase 1 (ALAS1) is a rate-limiting enzyme for heme biosynthesis in mammals. Heme is essential for the catalytic activities of P450 enzymes including steroid metabolic enzymes. Nuclear receptor 5A (NR5A) family proteins, steroidogenic factor-1 (SF-1), and liver receptor homolog-1 (LRH-1) play pivotal roles in regulation of steroidogenic enzymes. Recently, we showed that expression of SF-1/LRH-1 induces differentiation of mesenchymal stem cells into steroidogenic cells. In this study, genome-wide analysis revealed that ALAS1 was a novel SF-1-target gene in differentiated mesenchymal stem cells. Chromatin immunoprecipitation and reporter assays revealed that SF-1/LRH-1 up-regulated ALAS1 gene transcription in steroidogenic cells via binding to a 3.5-kb upstream region of ALAS1. The ALAS1 gene was up-regulated by overexpression of SF-1/LRH-1 in steroidogenic cells and down-regulated by knockdown of SF-1 in these cells. Peroxisome proliferator-activated receptor-γ coactivator-1α, a coactivator of nuclear receptors, also strongly coactivated expression of NR5A-target genes. Reporter analysis revealed that peroxisome proliferator-activated receptor-γ coactivator-1α strongly augmented ALAS1 gene transcription caused by SF-1 binding to the 3.5-kb upstream region. Finally knockdown of ALAS1 resulted in reduced progesterone production by steroidogenic cells. These results indicate that ALAS1 is a novel NR5A-target gene and participates in steroid hormone production.
Preconditioning of Stem Cells by Oxytocin to Improve Their Therapeutic Potential
Authors: Noiseux Nicolas , Borie Mélanie , Desnoyers Alexandra , Menaouar Ahmed , Stevens Louis Mathieu , Mansour Samer , Danalache Bogdan A. , Roy Denis-Claude , Jankowski Marek , Gutkowska Jolanta 
Published: October 2012

Abstract
Principal limitation of cell therapy is cell loss after transplantation because of the interplay between ischemia, inflammation, and apoptosis. We investigated the mechanism of preconditioning of mesenchymal stem cells (MSCs) with oxytocin (OT), which has been proposed as a novel strategy for enhancing therapeutic potential of these cells in ischemic heart. In this study, we demonstrate that rat MSCs express binding sites for OT receptor and OT receptor transcript and protein as detected by RT-PCR and immunofluorescence, respectively. In response to OT (10−10 to 10−6m) treatment, MSCs respond with rapid calcium mobilization and up-regulation of the protective protein kinase B (PKB or Akt) and phospho-ERK1/2 proteins. In OT-stimulated cells, phospho-Akt accumulates intracellularly close to the mitochondrial marker cytochrome c oxidase subunit 4. Functional analyses reveal the involvement of Akt/ERK1/2 pathways in cell proliferation, migration, and protection against the cytotoxic and apoptotic effects of hypoxia and serum deprivation. In addition, OT preconditioning increases MSC glucose uptake. Genes with angiogenic, antiapoptotic, and cardiac antiremodeling properties, such as heat shock proteins (hsps) HSP27, HSP32, HSP70, vascular endothelial growth factor, thrombospondin, tissue inhibitor of metalloproteinase (TIMP)-1, TIMP-2, TIMP-3, and matrix metalloproteinase-2, were also up-regulated upon OT exposure. Moreover, coculture with OT-preconditioned MSC reduces apoptosis, as measured using terminal transferase dUTP nick end labeling assay in newborn rat cardiomyocytes exposed to hypoxia and reoxygenation. In conclusion, these results indicate that OT treatment evokes MSC protection through both intrinsic pathways and secretion of cytoprotective factors. Ex vivo cellular treatment with OT represents an attractive strategy aimed to maximize the biological and functional properties of effector cells.
Reaction Pathways and Dynamics Effects for Ionizations of Vinyl Diazonium Ions
Authors: Mizutani Tomoyuki , Jinguji Masaru , Yamataka Hiroshi 
Published: October 2012

Abstract
The denitrogenation reactions of fifteen differently substituted vinyl diazonium (ethenediazonium) ions were examined by MO method at MP2/6-31G*. The parent vinyl diazonium ion (1, CH2=CH–N2+) was shown to initially give the H-bridged cation via the anti-H migration transition state (TS) or the syn-H migration TS. The relative barrier for the two TSs is very small, being 1.0 kcal mol−1 favoring the anti-H migration TS in free energy. The primary open cation is located on a very shallow minimum, and is 4.4 kcal mol−1 less stable than the bridged cation in free energy. The reactions of Me- and Ph-substituted vinyl diazonium ions showed characteristic features depending on the substituent. Molecular dynamics simulations for the reactions of 1 revealed that trajectories from the reactant state mostly gave the bridged cation as expected from the MO result, but there were trajectories that directly led to the open cation without H-participation, a clear manifestation of a dynamics effect. A dynamics effect on the relative population of the bridged versus the open cation is also presented.
ONIOM Study of a Proton Shuttle-Catalyzed Stepwise Mechanism for Peptide Bond Formation in the Ribosome
Authors: Fukushima Kazuaki , Iwahashi Hideo , Nishikimi Morimitsu 
Published: October 2012

Abstract
The process of protein synthesis occurs in the ribosome and is an essential feature of life. The exact reaction mechanism for peptide bond formation in the peptidyl transferase center of the ribosome is, however, still unknown. We calculated a stepwise mechanism of peptide bond formation, which is catalyzed by proton shuttles through cyclic hydrogen bonds, using the ONIOM (B3LYP/6-31G(d,p):Amber) method. In order to investigate the steric and electronic effects of the ribosomal environment on the reaction, we compared the geometries and energies of two model systems obtained either by ONIOM (B3LYP/6-31G(d,p):Amber) calculations or by cluster model calculations using the B3LYP/6-31G(d,p) level of theory. The results indicate that a steric effect of the ribosomal environment destabilizes the two transition states of the peptide bond formation, but that an electronic effect of the ribosomal environment as well as the catalytic shuttling of protons lowers the activation energy for the first step of the reaction.