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PubMed | University Hospital Center 1, Regional blood transfusion Center, Laboratory of Biochemistry and Molecular Biology, University Ibn Zohr and Pasteur Institute of Morocco
Type: Journal Article | Journal: Annales d'endocrinologie | Year: 2016

The present study aims at determining the relationship between the plasma fibrinogen concentration and the severity of coronary heart disease in type 2 diabetic patients.Prospective analytical survey, based on a sample of 120 subjects divided in four groups: 30 non diabetic coronary patients (G1), 30 coronary diabetic patients (G2), 30 non-coronary diabetic patients (G3), and 30 healthy subjects (G4).The average age was 59.587.88 years; female gender predominated by 52.5%. The plasma fibrinogen concentration corresponded to 3.46g/L0.86 in G1; 3.73g/L1.11 in G2; 3.06g/L0.98 in G3 and 2.46g/L0.51 in G4; with a significant difference between the four groups (P=0.001). The plasma fibrinogen concentration increased in parallel with the cardiovascular risk (P=0.0001); there was also a significant correlation between the plasma fibrinogen concentration and the clinical and para-clinical coronary disease severity (respectively P=0.005 and P=0.0001). A positive correlation between the plasma fibrinogen concentration and hyperglycemia (P=0.035) was found in G4. But no correlation with the lipids parameters, except for the low density-lipoproteins in G3 (P=0.035).In the Moroccan population, the plasma fibrinogen concentration was positively and significantly correlated with the coronary heart disease severity.


Cuny T.,Hoffmann-La Roche | Gerard C.,Hoffmann-La Roche | Saveanu A.,Hoffmann-La Roche | Saveanu A.,Laboratory of Biochemistry and Molecular Biology | And 4 more authors.
Annals of the New York Academy of Sciences | Year: 2011

In pituitary somatolactotroph cells, G protein-coupled receptors and receptor tyrosine kinases binding their specific ligands trigger an enzymatic cascade that converges to MAP kinase activation in the subcellular compartment. Different signaling pathways, such as AC/cAMP/PKA and PI3K/Akt pathways, interact with MAP kinase to regulate key physiological functions, such as hormonal secretion and cell proliferation. Abnormalities affecting these signaling pathways have been identified as preponderant factors of pituitary tumorigenesis. In addition to trans-sphenoidal surgery, somatostatin analogs are used to control hormonal hypersecretion in GH-secreting adenomas. However, a subset of these tumors remains uncontrolled with these treatFments, calling for new therapeutic approaches. In these cases, novel multivalent somatostatin analogs or new somatostatin-dopamine chimeric molecules could be of interest. Another attractive therapeutic approach may be to use one or several inhibitors acting downstream in the signaling pathway, such as mammalian target of rapamycin inhibitor. Cotargeting therapy and gene therapy are promising tools for these problematic pituitary tumors. © 2011 New York Academy of Sciences.


Hasnaoui N.,Higher Agronomic Institute | Hasnaoui N.,Tunis el Manar University | Mars M.,Higher Agronomic Institute | Chibani J.,Laboratory of Biochemistry and Molecular Biology | Trifi M.,Tunis el Manar University
Diversity | Year: 2010

The genetic diversity among Tunisian pomegranate cultivars has been investigated. Using universal primers, the random amplified polymorphic DNA (RAPD) method was used to generate banding profiles from a set of twelve cultivars. Data was then computed with appropriate programs to construct a dendrogram illustrating the relationships between the studied cultivars. Our data proved the efficiency of the designed method to examine the DNA polymorphism in this crop since the tested primers are characterized by a collective resolving power of 12.83. In addition, the cluster analysis has exhibited a parsimonious tree branching independent from the geographic origin of the cultivars. In spite of the relatively low number of primers and cultivars, RAPD constitutes an appropriate procedure to assess the genetic diversity and to survey the phylogenetic relationships in this crop. © 2010 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland.


Messaoudi S.,University of Nantes | Madi A.,University of Rouen | Prevost H.,University of Nantes | Feuilloley M.,University of Rouen | And 3 more authors.
Anaerobe | Year: 2012

Lactobacillus salivarius SMXD51 was previously isolated from the cecum of a Tunisian poultry and found to produce a bacteriocin-like substance highly active against the foodborne pathogen Campylobacter jejuni. The aim of this study was to examine some probiotic properties of the strain: acid and bile tolerance, capacity of adhesion, stimulation of immune defences (IL-6, IL-8, IL-10 and β-defensin 2), and modulation of the barrier integrity. The results showed that L. salivarius SMXD51 can tolerate gastrointestinal conditions (acid and bile), adhere to intestinal cells and stimulate the immune system. The bacterium strengthened the intestinal barrier functions through the increase of the transepithelial electrical resistance (TEER) and reinforcement of the F-actin cytoskeleton. One hour pretreatment with L. salivarius SMXD51 protected against Pseudomonas aeruginosa PAO1-induced decrease of TEER and damage of the F-actin cytoskeleton. Our results highlight that L. salivarius SMXD51 fulfils the principle requirements of an efficient probiotic and may be seen as a reliable candidate for further validation studies in chicken. © 2012 Elsevier Ltd.


As part of a process that regulates gene expression, the molecular machinery responsible for transcribing DNA into RNA stalls. Robert G. Roeder (left), Ming Yu (right), and their collaborators have described the protein complex that restarts this machinery. Credit: Zach Veilleux/The Rockefeller University There are about 20,000 genes in the human genome, but not all are used in all cells at all times. At any given moment, a cell is converting only roughly half its genes into proteins. And of those active genes, about 75 percent are regulated by a process known as 'RNA polymerase pausing.' This critical from of gene regulation occurs when an enzyme that transcribes the DNA hesitates at the beginning of the gene. Much like a runner at the start of a race, this molecular machine is poised to take off, but waits for the official signal. In work published on Dec. 11 in Science, Rockefeller University researchers and their collaborators describe a critical new regulator that helps restart a stalled RNA polymerase. The research, led by Robert G. Roeder, Arnold and Mabel Beckman Professor and head of Rockefeller's Laboratory of Biochemistry and Molecular Biology, helps to explain how some of the most promising new cancer therapeutics act in the cell and could facilitate future drug development. The human body is made up of more than 200 different cell types, and the specific complement of genes that are active defines one cell type from another. A skin cell uses different genes than a neuron, just as a healthy cell activates different genes than a leukemia cell. Because gene regulation is so important, the cell uses a highly intricate, multi-step process to convert the genes encoded in our DNA into proteins. In one of the earliest steps, a molecular machine called RNA polymerase II races along the gene, transcribing the DNA letters into a message, RNA, that can later be translated into proteins. More than a decade ago, researchers discovered that RNA polymerase II can pause at the beginning of genes. "Most cells use around half their 20,000 genes at any given time," explains co-first author Ming Yu, a postdoc in the lab. "RNA Polymerase II is paused at about 75 percent of those genes, making it a very important form of gene regulation for the cell." In the recent study, the team sought to identify new regulators that release the paused polymerase. They identified a complex of six proteins, known as PAF1C, that is essential for the polymerase to launch across the gene. "In the past, researchers thought that PAF1C functioned much later in transcription," says Roeder, "but we have found a novel role for the complex at the very beginning, in the release of the poised transcription machinery." In experiments in which they reduced PAF1C levels in cells, the team found that RNA polymerase II failed to release and remained paused at the start of the gene. The extended pause has a significant effect on gene expression. "We found that reducing PAF1C affected pausing on more than 5,000 genes," says Yu, "and that this in turn resulted in significant changes in expression levels for many of these genes." This work has implications beyond understanding how genes are regulated, according to the researchers. Several promising cancer therapeutics in clinical trials, most notably for certain leukemias, inhibit key regulators of polymerase pausing. "Our study offers further insight into how those inhibitors work," says Roeder, "and it is likely that this knowledge will facilitate the development of more specific inhibitors that fight cancer by targeting additional aspects of polymerase pausing and release." More information: "RNA polymerase II–associated factor 1 regulates the release and phosphorylation of paused RNA polymerase II", Science, www.sciencemag.org/lookup/doi/10.1126/science.aad2338


Bayoub K.,Hassan II University | Baibai T.,Hassan II University | Mountassif D.,Laboratory of Biochemistry and Molecular Biology | Retmane A.,Laboratory of Synthesis | Soukri A.,Hassan II University
African Journal of Biotechnology | Year: 2010

Searches for substances with antimicrobial activity are frequent and medicinal plants have beenconsidered interesting by some researchers since they are frequently used in popular medicine as remedies for many infectious diseases. The aim of this study was to verify the antibacterial effect of ethanol extracts of 13 plants (Artemisia Herba Alba, Lavandula officinalis L., Matricaria Chamomilla, Eugenia caryophylata, Cistus salvifolius, Mentha suaveolens subsp. Timija, Thymus serpyllum L.Lippia citriodora, Cinnamomum Zeylanicum, Rosa centifolia, Thymus vulgaris L, Rosmarinus officinalis and Pelargonium graveolens) against Listeria monocytogenes and other pathogenic strains. These plants are used more for their therapeutic effects in the aromatization of the traditionally fermented dairy products. For this purpose, the agar well diffusion method was the antimicrobial susceptibility performed test. The major components of extracts tested were identified by gas chromatography coupled with mass spectrometry (GC/MS) analysis. The obtained results revealed in vitro anti-Listeria monocytogenes activities of all the extracts. Also, the extracts of clove, mint timija, cinnamon, cistus, rose, thyme, wild thyme, artemisia, rosemary, geranium and camomile presented in this order promises inhibitory capacity with MIC value between 0.25 mg/mL for clove extract and 6.75 mg/mL for chamomile extract. On the other hand, the antimicrobial activity was mainly a function of their chemical composition, in particular in the nature of their major volatile compounds. This study thus confirmed the possibility of using these plants or some of their components in food systems to prevent the growth of foodborne bacteria and to extend the shelf-life of processed foods. © 2010 Academic Journals.


Deharo J.-C.,Timone University Hospital | Guieu R.,Timone University Hospital | Guieu R.,Aix - Marseille University | Mechulan A.,Timone University Hospital | And 7 more authors.
Journal of the American College of Cardiology | Year: 2013

Objectives This study sought to investigate the clinical and laboratory findings of patients affected by sudden-onset syncope without prodromes who had a normal heart and normal electrocardiogram. Background The pathophysiology of syncope in these patients is uncertain. Methods We compared the clinical and laboratory findings of 15 patients with sudden-onset syncope without prodromes who had a normal heart and normal electrocardiogram (the study group) with those of 31 patients with established vasovagal syncope (VVS). Results The patients in the study group were older than those with VVS (age 61 ± 12 years vs. 46 ± 17 years) and had a history of fewer episodes of syncope (median of 2 [interquartile range [IQR]: 1 to 2.5] vs. 9 [IQR: 4 to 15] years) that were of more recent onset (median of 1 [IQR: 0 to 1] vs. 10.5 [IQR: 3.3 to 27] years). The study group had lower median baseline adenosine plasmatic levels than the VVS group (0.25 μmol/l [95% confidence interval: 0.10 to 1.51] vs. 0.85 μmol/l [95% confidence interval: 0.32 to 2.80]). On receiver-operating characteristic curve analysis, the adenosine plasmatic level of ≤0.36 best discriminated between groups, displaying 73% sensitivity and 93% specificity. Tilt table testing was more frequently positive in patients with VVS than in the study group (74% vs. 33%). A similarly high positivity rate of adenosine/adenosine triphosphate testing was found in both groups. Conclusions Common clinical features and a low adenosine plasmatic level define a distinct form of syncope, distinguish it from VVS, and suggest a causal role of the adenosine pathway. © 2013 by the American College of Cardiology Foundation Published by Elsevier Inc.


Luk E.,Laboratory of Biochemistry and Molecular Biology | Ranjan A.,Laboratory of Biochemistry and Molecular Biology | FitzGerald P.C.,U.S. National Institutes of Health | Mizuguchi G.,Laboratory of Biochemistry and Molecular Biology | And 3 more authors.
Cell | Year: 2010

Histone variant H2A.Z-containing nucleosomes are incorporated at most eukaryotic promoters. This incorporation is mediated by the conserved SWR1 complex, which replaces histone H2A in canonical nucleosomes with H2A.Z in an ATP-dependent manner. Here, we show that promoter-proximal nucleosomes are highly heterogeneous for H2A.Z in Saccharomyces cerevisiae, with substantial representation of nucleosomes containing one, two, or zero H2A.Z molecules. SWR1-catalyzed H2A.Z replacement in vitro occurs in a stepwise and unidirectional fashion, one H2A.Z-H2B dimer at a time, producing heterotypic nucleosomes as intermediates and homotypic H2A.Z nucleosomes as end products. The ATPase activity ofSWR1 is specifically stimulated by H2A-containing nucleosomes without ensuing histone H2A eviction. Remarkably, further addition of free H2A.Z-H2B dimer leads to hyperstimulation of ATPase activity, eviction of nucleosomal H2A-H2B, and deposition of H2A.Z-H2B. These results suggest that the combination of H2A-containing nucleosome and free H2A.Z-H2B dimer acting as both effector and substrate for SWR1 governs the specificity and outcome of the replacement reaction. © 2010 Elsevier Inc.


Formisano-Treziny C.,French Institute of Health and Medical Research | Formisano-Treziny C.,Aix - Marseille University | De San Feliciano M.,French Institute of Health and Medical Research | Gabert J.,French Institute of Health and Medical Research | Gabert J.,Laboratory of Biochemistry and Molecular Biology
Journal of Molecular Diagnostics | Year: 2012

MicroRNAs (miRNAs) are small noncoding RNAs of approximately 18 to 25 nucleotides in length that negatively regulate gene expression via either the degradation or translational inhibition of their target mRNAs. Because miRNAs are essential for the regulation of critical physiological processes as well as a variety of pathological events, they have emerged as a novel class of molecular diagnostic biomarkers and therapeutic agents or targets. Accordingly, the need for novel methods for the quantification of miRNA has increased due to interest in their clinical implications. Currently, real-time quantitative polymerase chain reaction (qPCR) is considered the most robust technology for nucleic acid quantification. Different tools for miRNA quantification by using qPCR are now commercially available, but only relative quantification strategies have been reported. This situation may be partly due to the difficulty in obtaining an appropriate molecule with which to establish an miRNA calibration range. Here, we describe a rapid and convenient strategy for the development of a calibrator, which enables the absolute quantification of miRNAs by using qPCR and allows the cloning of a synthetic sequence of interest instead of a PCR product into a plasmid. Copyright © 2012 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.


Fabrias G.,CSIC - Institute of Advanced Chemistry of Catalonia | Munoz-Olaya J.,CSIC - Institute of Advanced Chemistry of Catalonia | Cingolani F.,CSIC - Institute of Advanced Chemistry of Catalonia | Signorelli P.,Laboratory of Biochemistry and Molecular Biology | And 3 more authors.
Progress in Lipid Research | Year: 2012

Sphingolipids are a wide family of lipids that share common sphingoid backbones, including (2S,3R)-2-amino-4-octadecane-1,3-diol (dihydrosphingosine) and (2S,3R,4E)-2-amino-4-octadecene-1,3-diol (sphingosine). The metabolism and biological functions of sphingolipids derived from sphingosine have been the subject of many reviews. In contrast, dihydrosphingolipids have received poor attention, mainly due to their supposed lack of biological activity. However, the reported biological effects of active site directed dihydroceramide desaturase inhibitors and the involvement of dihydrosphingolipids in the response of cells to known therapeutic agents support that dihydrosphingolipids are not inert but are in fact biologically active and underscore the importance of elucidating further the metabolic pathways and cell signaling networks involved in the biological activities of dihydrosphingolipids. Dihydroceramide desaturase is the enzyme involved in the conversion of dihydroceramide into ceramide and it is crucial in the regulation of the balance between sphingolipids and dihydrosphingolipids. Furthermore, given the enzyme requirement for O 2 and the NAD(P)H cofactor, the cellular redox balance and dihydroceramide desaturase activity may reciprocally influence each other. In this review both dihydroceramide desaturase and the biological functions of dihydrosphingolipids are addressed and perspectives on this field are discussed. © 2012 Elsevier Ltd. All rights reserved.

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