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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
Fri Jul 01 2022
Journal Name
Journal Of Molecular Structure
Interaction behavior of curcumin encapsulated onto functionalized SBA-15 as an efficient carrier and release in drug delivery
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In this work, mesoporous silica SBA-15 was prepared and functionalized with amine groups (i.e., NH2) to form NH2/SBA-15. The curcumin (CUR) was encapsulated into the surface and pore of NH2/SBA-15 to create CUR@NH2/SBA-15 as an efficient carrier in drug delivery systems (DDSs). The three samples (i.e., SBA-15, NH2/SBA-15, and CUR@NH2/SBA-15) were characterized. The study investigated the effect of the carrier dose, initial CUR concentration, pH, and contact time on the CUR loading efficiency (DLE%) via adsorption. The best DLE% for the SBA-15 and NH2/SBA-15 were found to be 45% and 89.7%, respectively. The Langmuir isotherm had a greater correlation coefficient (R2) of 0.998 for SBA-15. A pseudo-secondorder kinetic model seemed to fit well

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Publication Date
Wed Nov 04 2015
Journal Name
Journal Of Chemical, Biological And Physical Sciences
The Effect of Alkaloid Extracted from Cordia myxa Leaves on the Survival of Mustard Aphid Lipaphis erysimi (Kalt.)
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Publication Date
Tue Mar 28 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Efficacy, safety and Cardiovascular Disease Risk Lowering Ability of ACE Inhibitors, B-Blockers and Combination Antihypertensive Drug Regimes in Iraq
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Hypertension is a major health problem throughout the world because of its high prevalence and its association with increased risk of cardiovascular diseases. It is defined as systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg. The aim of this study was to compare the efficacy, safety and cardiovascular disease risk lowering ability, of three antihypertensive drug regimens.

A retrospective study was carried out on 66 hypertensive patients, divided in to three groups based on their antihypertensive drug regimens (ACE inhibitors, β-blockers treated and combination antihypertensive therapy, the combination therapy consist of two or more of the following antihypertensive drugs ACE inhibitor di

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Publication Date
Mon Jan 01 2018
Journal Name
Journal Of Pharmacy Research
Pulsatile drug delivery system - A review article
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Publication Date
Wed Apr 02 2025
Journal Name
Retos
Varied-method training and its effect on developing some functional physical abilities of youth basketball players
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Objective: Preparing training in a diverse style for young basketball players, and identifying the effect of training in a diverse style on some physical abilities (for young basketball players).Research methodology: the researchers chose the experimental method to know the research problem and its objectives, as it is represented by designing two equal groups, the control and the experimental, with pre- and post-tests. The study community was determined by youth basketball players for the 2023-2024 season, as the research community is (104) players, and a sample of (20) players was drawn from the youth category from Al-A'dhamiyah Sports Club, and it was chosen intentionally because they are the clubs most committed to training, as

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Publication Date
Mon Mar 01 2021
Journal Name
The Saudi Dental Journal
Development of patient information leaflets for fixed, removable, and functional appliances for Arabic-speaking orthodontic patients
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Publication Date
Wed Jun 15 2022
Journal Name
International Journal Of Agriculture Environment And Food Sciences
Functional and numerical response of Hippodamia variegata (Goeze) (Coleoptera: Coccinellidae) on Macrosiphum rosae (L.) (Hemiptera: Aphididae)
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In this study, functional and numerical response tests, which are important components in the selection of biological control agent, were carried out. In functional response trials, the amount of food consumed, attack rate (a) and handling time (Th) were calculated for each developmental period, depending on the number of preys given after 24 hours. The obtained results were evaluated with the Holling. In numerical response experiments, the development of the predator insect was examined depending on the number of preys given in certain numbers (5, 10, 20, 40 and 80) and the data were recorded. This phase of the trials continued until the individuals died. At this stage of the trials, the reproductive response of the p

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Publication Date
Mon Dec 22 2025
Journal Name
Journal Of Baghdad College Of Dentistry
Inhibition of bacterial growth around gutta percha cones by different antimicrobial solutions using antibiotic sensitivity test (An in vitro study)
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Background: Decontamination of gutta percha cones was important factor for success of root canal treatment. The aim of the present in vitro study was to identify and to compare the antimicrobial effect of following disinfection solutions: 0.2% chlorhexidine gluconate, Iodine, tetracycline hydrochloride solution, EDTA & formocresol mixed with zinc oxide eugenol, on E faecalis, E coli and Candida albicans using sensitivity test Materials and Methods: Three types of microorganisms were isolated from infected root canals (E faecalis, E coli and Candida albicans) and cultured on Mueller Hinton agar petri-dishes. Disinfection of gutta percha cones done by immersion in six disinfection solutions (six groups), the groups are: distill water (used a

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Publication Date
Mon Jun 07 2021
Journal Name
Journal Of Molecular Histology
Structural and functional relations between the connective tissue and epithelium of enamel organ and their role during enamel maturation
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Publication Date
Sun Feb 28 2021
Journal Name
Journal Of Economics And Administrative Sciences
The role of monetary policy in reducing inflation in Iraq through monetary sterilization mechanism. post-2003
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The main objective of the central bank is to achieve price stability and target in fractionates. Therefore, the bank sought to use modern tools and policies in order to reduce the negative effects of the accumulation of foreign reserves represented by monetary sterilization, similar to developed and developing countries alike, but with different available tools that are possible and imposed by the local financial and monetary environments, such as the window for buying and selling foreign currency, open market operations and deposit facilities. And lending existing. Because any in crease in the monetary base resulting from the accumulation of foreign reserves will affect price stability directly due to the consumer nature of the

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