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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 Jan 01 2021
Journal Name
Anais Da Academia Brasileira De Ciências
Molecular characterization of viruses associated to leaf curl disease complex on zucchini squash in Iraq reveals Deng primer set could distinguish between New and Old World Begomoviruses
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Publication Date
Mon Jul 01 2024
Journal Name
Journal Of The Faculty Of Medicine Baghdad
Evaluation of some Biochemical and Hematological Parameters in Patients with Chronic Kidney Disease
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Background: Chronic kidney disease is a condition that results from an indefinite change in the structure and function of the kidneys. A slow, steady progression characterizes it and is irreversible.  Objectives: This study aims to evaluate the findings of certain biochemical and hematological tests in samples from Iraqi CKD patients.  Methods: This study included 90 subjects, where 70 patients with chronic kidney disease and 20 healthy individuals. Blood samples were collected from the patients during their visits to Ghazi Al-Hariri Surgical Specialties' Hospital- Medical City, Baghdad, Iraq. Age, sex and body mass index were assessed for each participant followed by renal function tests [serum blood urea, creatinine, uric acid a

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Publication Date
Sun Mar 07 2010
Journal Name
Baghdad Science Journal
Safety method, Spectrophotometric Determination of Sulfamethaxazole drug in bulk and Pharmaceutical Preparations
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A simple, cheap, fast, accurate, Safety and sensitive spectrophotometric method for the determination of sulfamethaxazole (SFMx), in pure form and pharmaceutical dosage forms. has been described The Method is based on the diazotization of the drug by sodium nitrite in acidic medium at 5Cº followed by coupling with salbutamol sulphate (SBS) drug to form orange color the product was stabilized and measured at 452 nm Beer’s law is obeyed in the concentration range of 2.5-87.5 ?g ml-1 with molar absorptivity of 2.5x104 L mole-1 cm-1. All variables including the reagent concentration, reaction time, color stability period, and sulfamethaxazole /salbutamol ratio were studied in order to optimize the reaction conditions. No interferences were

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Publication Date
Sun Jan 01 2023
Journal Name
Journal Of Complementary Medicine Research
Principles and Advantages of New Drug Delivery Technologie
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Advanced drug delivery systems offer undeniable benefits for drug delivery. In the past three decades, new methods have been proposed to develop a novel carriers for drug delivery. Nowadays, the major goal is to maximize therapeutic benefit while minimizing side effects. Drug delivery technique is clearly shifting from the micro to nanoscale. Nano-drug delivery systems (NDDSs) are the most promising approach utilized to improve the accuracy of drug delivery and the efficacy of drugs.In this narrative review article, we evaluate how delivery challenges associated with commercial marketed products and discuss newer DDS is being carried out to overcome these challenges .Different colloidal carrier systems such as carbon nanotube ,li

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Publication Date
Wed Mar 29 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Effect of Some Storage Conditions upon the Survival of Some Fungal Spores
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Folic acid and multivitamin tablets containing Aspergillus flavus Penicillia spp. and Cladosporia spores were prepared at a compression pressure of 148 MN/m2 and stored at 35°C under different relative  humidifies (75,85, and 95)% within air tight containers, to study the effect of storage condition on them, as well as ,the estimation of the microbial level of the raw materials intended to be used in the two kinds of tablets . Result showed that some raw materials derived from natural origin were heavily contaminated with microorganism compared to that of synthetic origin ,the results also indicated the effect of relative humidity , types of fungal spore , and the hygroscopic nature of exicpient upon survival. Multivit

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Publication Date
Mon Jun 15 2020
Journal Name
Al-academy
Aesthetics of the Sufi Image and its Representations in Post-Modern Theater Show
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Publication Date
Sun Feb 03 2019
Journal Name
Journal Of The College Of Education For Women
The builds and functional relations Between the peopolitics and strategy
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The geopolities considering as build from the basies builds of the polities
geography, participating in appointing the military geography, and submit to it
geo-polities purveyed, playing important role to appointing the builds relations
between the high strategy and the military strategy, while the foreign polities of
the state, which considering as a tool for the state outside it environment and
borders playing the role of the performance and the functional works to the
peaceful or hostile reaction according to the geopolities purveyed which
participating in amassing the recourse for the economical, political, social,
military and technology strategies and activating it to achieving the state interests
and obj

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Publication Date
Mon Nov 05 2018
Journal Name
Iraqi National Journal Of Nursing Specialties
Evaluation and Comparison of Complete Dentures’ Complaints: Post-insertion
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Aims: This study aims to compare patients’ complaints and problems of wearing complete dentures.
Methodology: The sample included 40 Iraqi patients who are wearing complete dentures from about five years ago. They
were selected randomly with a age range between (55–65) years. The questions asked to the patients were listed according
to the recent classification of post-insertion problems.
Result: The results showed that the percentage of patient's complaint from adaptation problems (62.1%) was higher than
looseness problems (61.3%) and discomfort problems (39.3%) as followed.
Recommendation: Dentists need thorough knowledge of anatomy, physiology, pathology and psychology. The assessing
of the psyche and emotions

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Publication Date
Thu May 15 2025
Journal Name
Journal Of Animal Health And Production
Functional and Histological Study of Liver in Adult Rats Treated with Different Doses of Melatonin
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his study aimed to evaluate the effects of different doses of melatonin on liver function in adult rats. Eighteen Wistar adult albino rats (Rattus norvegicus), approximately 13–16 weeks old and weighing 230 ± 10 g, were randomly divided into three groups (n=6 per group) and treated orally for 30 days as follows: Group A1 received 10 mg/kg body weight (B.W) of melatonin; Group A2 received 20 mg/kg B.W of melatonin; and the control group (Group A) received distilled water. At the end of the treatment period, blood samples were collected via cardiac puncture, and serum was separated for biochemical analysis. Parameters assessed included oxidative stress markers (malondialdehyde (MDA), reduced glutathione (GSH)) and liver enzymes (aspa

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Publication Date
Tue Jan 01 2019
Journal Name
Indian Journal Of Public Health Research &amp; Development
Certain Hematological Denotations in Chronic Renal Failure Patients
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