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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
Mon Sep 11 2017
Journal Name
Journal Of Molecular Cell Biology
Sustained activation of P2X7 induces MMP-2-evoked cleavage and functional purinoceptor inhibition
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Publication Date
Tue Jan 16 2018
Journal Name
International Journal Of Science And Research
Some Biochemical Assays in Hemodialysis Patients with Chronic Hepatitis C
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Abstract: The present study aimed to evaluate calcium, potassium, albumin, protein, creatinine, urea, uric acid levels, and the level of total sialic acid in the sera of patients with chronic renal failure who had been infected with Hepatitis C virus and in the sera of patients with chronic renal failure, and compare them with healthy volunteers. A total of 90 subjects with age 25-55 years, were divided into three groups. G1 represents 30 patients with chronic renal failure who had treated by dialysis and infected with chronic Hepatitis C virus (positive group). G2 represents 30 patients with chronic failure who had been treated by dialysis (negative group), while G3 represents 30 healthy volunteers (control group). The results showed

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Publication Date
Sun Mar 07 2010
Journal Name
Baghdad Science Journal
Lymphocyte phenotyping in untreated children patients with chronic allergic asthma
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This study aimed to isolate and phenotype lymphocytes in untreated children patients with chronic allergic asthma. To reach such aim the study involved (25) patients from children (17 male and 9 female) whom their ages where between (3-10) years, in addition to (15) apparently healthy children (9 male and 6 female) in the same ages involved as control group. The data demonstrated that there was a significant increase in the mean percentages of T-lymphocytes (CD3+ cells) in the peripheral blood of patients (66.75±0.29)**, in comparison with control group (43.58±0.19), a significant increase in the mean percentages of T-helper lymphocytes (CD4+ cells) in the pe

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Publication Date
Tue Jun 15 2021
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Formulation and Characterization of Self-Microemulsifying Drug Delivery System of Tacrolimus
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Abstract

The present investigation aimed to formulate a liquid self-microemulsifying drug delivery system (SMEDDS) of tacrolimus to enhance its oral bioavailability by improving its dispersibility and dissolution rate. Four liquid SMEDDS were prepared using maisine CC as oil phase, labrasol ALF as surfactant and transcutol HP as co-surfactant based on the solubility studies of tacrolimus in these components. The phase behavior of the components and the area of microemulsion were evaluated using pseudoternary phase diagrams. The formulations were also assessed for thermodynamic stability, robustness to dilution, self-emulsification time, drug content, globule size and polydispersity index. The prepared SMEDDS formulations exhibi

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Publication Date
Tue Jan 01 2019
Wide-range tunable subwavelength band-stop filter for the far-infrared wavelengths based on single-layer graphene sheet
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Publication Date
Thu Feb 16 2023
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Drug Information Resources in Iraqi Community Pharmacies (Conference Paper) #
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Abstract

     Drug information resources are the information that is used in medications discovery, utilization, and management. Little information about different types of resources used by Iraqi community pharmacists is known. Therefore, the objectives were to determine drug information resources' type do the pharmacists used and the common drug information questions they faced during their work in community pharmacy. A cross-sectional descriptive study was conducted in different Iraqi provinces and online self-reported survey was introduced through Google Form Software to an appropriate sample of graduated pharmacists who were working in a private community pharmacy and having at least one

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Publication Date
Sun Feb 03 2019
Journal Name
Iraqi Journal Of Physics
Enhanced hydrogen gas sensitivity employing sputtered deposited NiO thin films
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Publication Date
Sun Apr 01 2018
Journal Name
Journal Of Educational And Psychological Researches
Relationship sensitivity to stress with positive mood Among Educational Counselors
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The study aimed to examine the sensitivity to stress and its relation to positive mood among educational supervisors. The researcher used the descriptive approach as more an appropriate method for the current study. The sample is composed of (200) educational supervisor. To collect study data, two scales have been used: one scale to measure the sensitivity to stress and the other to measure the positive mood. The results indicated that a high level of sensitivity to stress with low level of positive mood among educational supervisors, sensitivity to stress showed significant differences among the sample regarding to major. There is no correlation between sensitivity to stress and positive mood, and finally, there are no significant diffe

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Publication Date
Wed Jun 01 2016
Journal Name
Lap Lambert Academic Publishing
Schiff Base And Ligand Metal Complexes of Some Amino Acids and Drug
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Schiff Base And Ligand Metal Complexes of Some Amino Acids and Drug

Publication Date
Wed May 08 2019
Journal Name
Digest Journal Of Nanomaterials And Biostructures
IMPROVING SENSITIVITY OF In 2 O 3 AGAINST NO 2 TOXIC GAS BY LOADING TIN OXIDE
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The paper discusses the structural and optical properties of In 2 O 3 and In 2 O 3-SnO 2 gas sensor thin films were deposited on glass and silicon substrates and grown by irradiation of assistant microwave on seeded layer nucleated using spin coating technique. The X-ray diffraction revealed a polycrystalline nature of the cubic structure. Atomic Force Microscopy (AFM) used for morphology analysis that shown the grain size of the prepared thin film is less than 100 nm, surface roughness and root mean square for In 2 O 3 where increased after loading SnO 2 , this addition is a challenge in gas sensing application. Sensitivity of In 2 O 3 thin film against NO 2 toxic gas is 35% at 300 o C. Sensing properties were improved after adding Tin Oxi

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