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21.
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Contribution of PTPN22, CD28, CTLA-4 and ZAP-70 variants to the risk of type 1 diabetes in Tunisians
Ferjeni Zouidi Mouna Stayoussef Dorra Bouzid Hajer Fourati Olfa Abida M. Ben Ayed Thouraya Kammoun Monjia Hachicha Carlos Penha-Gonçalves Hatem Masmoudi 《Gene》2014
Type 1 diabetes (T1D) is caused by an immune-mediated destruction of the insulin-producing β-cells. Several studies support the involvement of T cell activation molecules. In order to underline the role of the genes involved in this pathway, we investigated, using the Sequenom MassARRAY platform, polymorphisms of sixteen single-nucleotide polymorphisms (SNPs) belonging to PTPN22, CD28, CTLA-4, and ZAP-70 genes in 76 T1D patients and 162 unrelated healthy controls from Southern Tunisia. 相似文献
23.
Anti-DNA antibodies: structure and pathogenic role 总被引:2,自引:0,他引:2
Ayed K 《Archives de l'Institut Pasteur de Tunis》2000,77(1-4):3-9
Anti DNA antibodies are generally classified into two major groups: Anti ds DNA (anti double .. stranded DNA) antibody and anti ss-DNA (anti single-stranded DNA) antibody. Anti-ds DNA antibodies are highly specific to systemic lupus erythematosus (SLE) and are probably involved in the pathogenesis of lupus nephritis. There are numerous serological tests for detecting anti-ds DNA. The detection of anti-ds DNA antibodies in the circulation of patients is one of the major criteria for the diagnosis of SLE; moreover, exacerbation of the disease are proceeded by increasing anti-DNA levels and the development of lupus nephritis, one of the most serious complications of the disease, strongly correlates with the presence of high avidity anti-DNA. It was reported that even normal individuals express anti-ds DNA. However, anti ds DNA found in healthy individuals is usually of the immunoglobulin M (IgM) isotype and shows a low affinity to ds-DNA. These natural antibodies are characterized by a wide cross-reactivity and are usually encoded by gene segments in the germ line configuration. In contrast, the ds-DNA antibodies involved influenced by various findings supporting the proposition that anti-ds DNA is involved in the pathogenesis of SLE, an enormous amount of scientific investigation has failed to reveal the exact mechanism through which this occurs. 相似文献
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25.
Harry W. Duckworth Nham T. Nguyen Yin Gao Lynda J. Donald Robert Maurus Ayeda Ayed Brigitte Bruneau Gary D. Brayer 《Biochimica et Biophysica Acta - Proteins and Proteomics》2013,1834(12):2546-2553
The citrate synthase (CS) of Escherichia coli is an allosteric hexameric enzyme specifically inhibited by NADH. The crystal structure of wild type (WT) E. coli CS, determined by us previously, has no substrates bound, and part of the active site is in a highly mobile region that is shifted from the position needed for catalysis. The CS of Acetobacter aceti has a similar structure, but has been successfully crystallized with bound substrates: both oxaloacetic acid (OAA) and an analog of acetyl coenzyme A (AcCoA). We engineered a variant of E. coli CS wherein five amino acids in the mobile region have been replaced by those in the A. aceti sequence. The purified enzyme shows unusual kinetics with a low affinity for both substrates. Although the crystal structure without ligands is very similar to that of the WT enzyme (except in the mutated region), complexes are formed with both substrates and the allosteric inhibitor NADH. The complex with OAA in the active site identifies a novel OAA-binding residue, Arg306, which has no functional counterpart in other known CS-OAA complexes. This structure may represent an intermediate in a multi-step substrate binding process where Arg306 changes roles from OAA binding to AcCoA binding. The second complex has the substrate analog, S-carboxymethyl-coenzyme A, in the allosteric NADH-binding site and the AcCoA site is not formed. Additional CS variants unable to bind adenylates at the allosteric site show that this second complex is not a factor in positive allosteric activation of AcCoA binding. 相似文献
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Shams Tabrez Fazlur Rahman Rahat Ali Abdulaziz
S. Alouffi Sajjadul
Kadir Akand Bader
Mohammed Alshehri Fahdah
Ayed Alshammari Aftab Alam Mohammed
A. Alaidarous Saeed Banawas Abdul Aziz
Bin Dukhyil Abdur Rub 《Bioscience reports》2021,41(1)
Cynaroside, a flavonoid, has been shown to have antibacterial, antifungal and anticancer activities. Here, we evaluated its antileishmanial properties and its mechanism of action through different in silico and in vitro assays. Cynaroside exhibited antileishmanial activity in time- and dose-dependent manner with 50% of inhibitory concentration (IC50) value of 49.49 ± 3.515 µM in vitro. It inhibited the growth of parasite significantly at only 20 µM concentration when used in combination with miltefosine, a standard drug which has very high toxicity. It also inhibited the intra-macrophagic parasite significantly at low doses when used in combination with miltefosine. It showed less toxicity than the existing antileishmanial drug, miltefosine at similar doses. Propidium iodide staining showed that cynaroside inhibited the parasites in G0/G1 phase of cell cycle. 2,7-dichloro dihydro fluorescein diacetate (H2DCFDA) staining showed cynaroside induced antileishmanial activity through reactive oxygen species (ROS) generation in parasites. Molecular-docking studies with key drug targets of Leishmania donovani showed significant inhibition. Out of these targets, cynaroside showed strongest affinity with uridine diphosphate (UDP)-galactopyranose mutase with −10.4 kcal/mol which was further validated by molecular dynamics (MD) simulation. The bioactivity, ADMET (absorption, distribution, metabolism, excretion and toxicity) properties, Organisation for Economic Co-operation and Development (OECD) chemical classification and toxicity risk prediction showed cynaroside as an enzyme inhibitor having sufficient solubility and non-toxic properties. In conclusion, cynaroside may be used alone or in combination with existing drug, miltefosine to control leishmaniasis with less cytotoxicity. 相似文献
28.
Boubaker Nouha Setti Spagnuolo Manuela Trabelsi Nesrine Said Rahma Gurtner Aymone Regazzo Giulia Ayed Haroun Blel Ahlem Karray Omar Saadi Ahmed Rammeh Soumaya Chebil Mohamed Rizzo Maria Giulia Piaggio Giulia Ouerhani Slah 《Molecular biology reports》2020,47(2):1283-1292
Molecular Biology Reports - Hsa-mir-143 and hsa-let-7c have been reported to be deregulated in multiple neoplasms. The main purpose of this study was to investigate the expression of these miRNAs... 相似文献
29.
Background
Given the high occurrence of prostate cancer worldwide and one of the major sources of the discovery of new lead molecules being medicinal plants, this research undertook to investigate the possible anti-cancer activity of two natural cycloartanes; cycloartane-3,24,25-diol (extracted in our lab from Tillandsia recurvata) and cycloartane-3,24,25-triol (purchased). The inhibition of MRCKα kinase has emerged as a potential solution to restoring the tight regulation of normal cellular growth, the loss of which leads to cancer cell formation.Methods
Kinase inhibition was investigated using competition binding (to the ATP sites) assays which have been previously established and authenticated and cell proliferation was measured using the WST-1 assay.Results
Cycloartane-3,24,25-triol demonstrated strong selectivity towards the MRCKα kinase with a Kd50 of 0.26 μM from a total of 451 kinases investigated. Cycloartane-3,24,25-triol reduced the viability of PC-3 and DU145 cell lines with IC50 values of 2.226?±?0.28 μM and 1.67?±?0.18 μM respectively.Conclusions
These results will prove useful in drug discovery as Cycloartane-3,24,25-triol has shown potential for development as an anti-cancer agent against prostate cancer. 相似文献30.
The highly similar Arabidopsis homologs of trithorax ATX1 and ATX2 encode proteins with divergent biochemical functions 总被引:3,自引:0,他引:3
Saleh A Alvarez-Venegas R Yilmaz M Le O Hou G Sadder M Al-Abdallat A Xia Y Lu G Ladunga I Avramova Z 《The Plant cell》2008,20(3):568-579
Gene duplication followed by functional specialization is a potent force in the evolution of biological diversity. A comparative study of two highly conserved duplicated genes, ARABIDOPSIS TRITHORAX-LIKE PROTEIN1 (ATX1) and ATX2, revealed features of both partial redundancy and of functional divergence. Although structurally similar, their regulatory sequences have diverged, resulting in distinct temporal and spatial patterns of expression of the ATX1 and ATX2 genes. We found that ATX2 methylates only a limited fraction of nucleosomes and that ATX1 and ATX2 influence the expression of largely nonoverlapping gene sets. Even when coregulating shared targets, ATX1 and ATX2 may employ different mechanisms. Most remarkable is the divergence of their biochemical activities: both proteins methylate K4 of histone H3, but while ATX1 trimethylates it, ATX2 dimethylates it. ATX2 and ATX1 provide an example of separated K4 di from K4 trimethyltransferase activity. 相似文献