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Epigenome-wide analysis reveals functional modulators of drug sensitivity and post-treatment survival in chronic lymphocytic leukaemia
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Abstract<sec> <title>Background

Chronic lymphocytic leukaemia (CLL) patients display a highly variable clinical course, with progressive acquisition of drug resistance. We sought to identify aberrant epigenetic traits that are enriched following exposure to treatment that could impact patient response to therapy.

Methods

Epigenome-wide analysis of DNA methylation was performed for 20 patients at two timepoints during treatment. The prognostic significance of differentially methylated regions (DMRs) was assessed in independent cohorts of 139 and 163 patients. Their functional role in drug sensitivity was assessed in vitro.

Results

We identified 490 DMRs following exposure to therapy, of which 31 were CLL-specific and independent of changes occurring in normal B-cell development. Seventeen DMR-associated genes were identified as differentially expressed following treatment in an independent cohort. Methylation of the HOXA4, MAFB and SLCO3A1 DMRs was associated with post-treatment patient survival, with HOXA4 displaying the strongest association. Re-expression of HOXA4 in cell lines and primary CLL cells significantly increased apoptosis in response to treatment with fludarabine, ibrutinib and idelalisib.

Conclusion

Our study demonstrates enrichment for multiple CLL-specific epigenetic traits in response to chemotherapy that predict patient outcomes, and particularly implicate epigenetic silencing of HOXA4 in reducing the sensitivity of CLL cells to therapy.

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Publication Date
Tue Jun 05 2018
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Preparation and characterization of timed drug delivery system of sumatriptan using natural polymers
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Pulsatile drug delivery systems are time-controlled dosage forms which are designed to release the active pharmaceutical ingredient after a predetermined lag time to synchronize the disease circadian rhythm. A migraine shows circadian rhythm with a marked increase in attacks between 6 a.m. and 8 a.m.

Sumatriptan is a selective agonist at serotonin (5-Hydroxy tryptamine1  (5-HT1))receptors, is an effective treatment for acute migraine attacks.

The aim of this work is to prepare time-controlled press-coated tablet with a lag time of 5.45 hrs.

Six formulas of fast dissolving core tablets and three formulas of press-coated tablets were prepared by using direct compression method using different variables to prepa

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Publication Date
Thu Jan 01 2015
Journal Name
World Journal Of Experimental Biosciences
Evaluation of anti-Helicobacter pylori antibodies level in sera of patients with chronic hepatitis B
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The relationship between chronic hepatitis B virus and Helicobacter pylori infection was evaluated to determine, seventy five patients with chronic hepatitis B infection (8-70 years) were investigated. The results were compared with the results of 50 healthy volunteers. Anti-H. pylori antibodies IgA and IgG were measured by Indirect fluorescent antibody test (IFAT) in sera of patients and healthy groups. The percentage of anti-H.pylori IgA antibodies (26.67%) were significantly (P<0.01) higher than healthy control group. While, no significant difference was found between the percentages of anti-H. pylori IgG antibodies (48 %) in patient sera and these kind of antibodies in sera of healthy control group (P > 0.05). The present results indica

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Publication Date
Tue Jul 29 2025
Journal Name
Al-rafidain University College For Sciences
Uncertainty types and theories of treatment
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In this research the researcher had the concept of uncertainty in terms of types and theories of treatment and measurement as it was taken up are three types of indeterminacy and volatility and inconsistency

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Publication Date
Wed Mar 10 2021
Journal Name
Baghdad Science Journal
Heun Method Using to Solve System of NonLinear Functional Differential Equations
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In this paper Heun method has been used to find numerical solution for first order nonlinear functional differential equation. Moreover, this method has been modified in order to treat system of nonlinear functional differential equations .two numerical examples are given for conciliated the results of this method.

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Publication Date
Mon Dec 17 2018
Journal Name
Iop Conference Series: Materials Science And Engineering
Differentiation of CD34+ Human Hair Follicle Stem Cells into Functional Melanocytes
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Publication Date
Wed Aug 01 2018
Journal Name
Journal Of Pharmaceutical Sciences
Schiff base complexes of some drug substances (Review)
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Schiff bases (SBs) represent multipurpose ligands that can be prepared from the concentration of prime amines with carbonyl clusters. Creation of SB transition metal compounds via as ligands has opportunity of attaining coordination complexes of abnormal arrangement and stability. These transition metal compounds have extraordinary attention as a consequence of their dynamic portion in metalloenzymes and as biomimetic prototypical complexes as a result of their proximity to usual enzymes and proteins. These complexes are imperative in medicinal disciplines owing to their widespread range of biological actions. They mostly exhibit organic actions involving antifungal, antibacterial, antitumor, antidiabetic, herbicidal, antiproliferative, ant

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Publication Date
Sun Jun 05 2016
Journal Name
Baghdad Science Journal
Synthesis, Characterization of Derivatives Tetrazoles for Trimethoprim Drug
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The present work involved synthesis of serval new substituted tetrazole via Schiff bases for trimethoprim drug by two steps. The first step involved direct reaction of different ketones and aldehydes with trimethoprim producing the corresponding Schiff bases (1-10), whereas the second step, involved preparation new tetrazoles derivatives (11-20) through reaction of the ready Schiff bases (in the first step) with sodium azidein in dioxin. The prepared compounds were characterized by UV, FT-IR, and some of them by 13C-NMR, 1H-NMR spectroscopy and physical properties.

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Publication Date
Tue Aug 28 2018
Journal Name
Journal Of Pharmaceutical Sciences And Research
Schiff base complexes of some drug substances (Review)
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Schiff bases (SBs) represent multipurpose ligands that can be prepared from the concentration of prime amines with carbonyl clusters. Creation of SB transition metal compounds via as ligands has opportunity of attaining coordination complexes of abnormal arrangement and stability. These transition metal compounds have extraordinary attention as a consequence of their dynamic portion in metalloenzymes and as biomimetic prototypical complexes as a result of their proximity to usual enzymes and proteins. These complexes are imperative in medicinal disciplines owing to their widespread range of biological actions. They mostly exhibit organic actions involving antifungal, antibacterial, antitumor, antidiabetic, herbicidal, antiproliferative, ant

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Publication Date
Fri Dec 31 2021
Journal Name
Iraqi Journal Of Laser
The influence of no-core fibre length on the sensitivity Optical fibre Humidity sensor
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Abstract: Reflection optical fibre Humidity sensor is presented in this work, which is based on no core fibre prepared by splicing a segment of no core fibre (NCF) at different lengths 1-6 cm with fixed diameter 125 µm and a single mode fibre (SMF). The range of humidity inside the chamber is controlled from 30% to 90% RH at temperature ~ 30 °С. The experimental result shows that the resonant wavelength dip shift decreases linearly with an increment of RH% and the sensitivity of the sensor increased linearly with an increasing in the length of NCF. However, a high sensitivity 716.07pm/RH% is obtained at length 5cm with good stability and reputability.  Furthermore, the sensor is shif

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Publication Date
Mon Feb 28 2022
Journal Name
Structural Chemistry
Sensitivity of SnO2 nanoparticles/reduced graphene oxide hybrid to NO2 gas: A DFT study
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Abstract<p>The sensitivity of SnO<sub>2</sub> nanoparticles/reduced graphene oxide hybrid to NO<sub>2</sub> gas is discussed in the present work using density functional theory (DFT). The SnO<sub>2</sub> nanoparticles shapes are taken as pyramids, as proved by experiments. The reduced graphene oxide (rGO) edges have oxygen or oxygen-containing functional groups. However, the upper and lower surfaces of rGO are clean, as expected from the oxide reduction procedure. Results show that SnO<sub>2</sub> particles are connected at the edges of rGO, making a p-n heterojunction with a reduced agglomeration of SnO2 particles and high gas sensitivity. The DFT results are in</p> ... Show More
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