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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 Jan 01 2019
Journal Name
Journal Of Global Pharma Technology
Synthesis and characterization of chitosan schiff base hydrogel for controlled drug release
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Chitosan-schiff base with three different ratios of para-Dimethyl aminobenzaldehyde& chitosan Schiff base hydrogels have been prepared for controlled drug release study. The synthesized chitosan Schiff base and chitosan Schiff base hydrogel were characterized by FT-IR, UV-Visible, SEM, analysis. Swelling properties of the hydrogel were investigated at three different media pH (2, 7, 10). The swelling degree varied with the pH, amount of crosslinking agent glutaraldehyde and with the amount of paraDimethylaminobenzaldehyde for the hydrogels. All hydrogels were used for controlled drug release system. Aspirin was used as model drug, in three different buffer solution (2, 7, 10) as release media. The rate of release of drugs in the pH2 is m

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Publication Date
Wed Jul 14 2021
Journal Name
Annals Of R.s.c.b.
Synthesis, Characterization and Biological Activity of heterocyclic compounds derived from Amoxcilline drug.
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A first step in this research was to synthesize Schiff's bases(1-3)using an Amoxcilline intensification reaction with different aromatic aldehydes in absolute ethanol. In benzene and refluxing conditions,Schiff's bases were cyclized with succinic and Phthalic anhydride to give a new sequence of 1,3-oxazepine derivatives(4-6) and (7-9),respectively.The last step,cyclization reactions with sodium azide in THF solvent resulted in the formation of [10 and 11], which are supposed to be biologically significant.FT.IR, 1H-NMR and 13C-NMR (for compound 4,7,9, and 11),as well as melting points reported, were used to characterize these prepared compounds ,Bacillus (G+), Staphylococcus (G+), and E.Coli (G-)were screened against these compounds. . To i

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Publication Date
Thu Jun 25 2020
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Formulation and Characterization of Piroxicam as Self-Nano Emulsifying Drug Delivery System
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Piroxicam (PIR) is a nonsteroidal anti-inflammatory drug of oxicam category, used in gout, arthritis, as well as other inflammatory conditions (topically and orally). PIR is practically insoluble in water, therefore the aim is prepare and evaluate piroxicam as liquid self-nanoemulsifying drug delivery system to enhance its dispersibility and stability. The Dispersibilty and Stability study have been conducted in Oil, Surfactant and Co-surfactant for choosing the best materials to dissolve piroxicam. The pseudo ternary phase diagrams have been set at 1:1, 2:1, 3:1 as well as 4:1 ratio of surfactants and co-surfactants, also there are 4 formulations were prepared by using various concentrations of transcutol HP, cremophore EL and triacetin

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Publication Date
Sat Apr 01 2023
Journal Name
Journal Of Environmental Accounting And Management
On the Food Chain Model with Sokol Howell Functional Response and Prey Refuge
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The cheif aim of the present investigation is to develop Leslie Gower type three species food chain model with prey refuge. The intra-specific competition among the predators is considered in the proposed model. Besides the logistic growth rate for the prey species, Sokol Howell functional response for predation is chosen for our model formulation. The behaviour of the model system thoroughly analyses near the biologically significant equilibria. The linear stability analysis of the equilibria is carried out in order to examine the response of the system. The present model system experiences Hopf bifurcation depending on the choice of suitable model parameters. Extensive numerical simulation reveals the validity of the proposed model.

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Publication Date
Sat Dec 31 2016
Journal Name
Al-kindy College Medical Journal
Diagnostic Value Of Post Exercise Systolic Blood Pressure Response In Ischemic Heart Disease
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 Background: The normal decline in systolic blood pressure during recovery phase of treadmill exercise dose not occur in most patients with coronary artery disease, in others recovery values systolic blood pressure may even exceed the peak exercise value. Objectives: Treadmill exercise test parameters indicating the presence and extent of coronary artery disease have traditionally included such as exercise duration, blood pressure and ST-segment response to exercise. The three –minute systolic blood pressure ratio is another important indicator of presence and significance of coronary artery disease is useful and obtainable measure that can be applied in all patients who are undergoing stress testing for evaluation of suspected is

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Publication Date
Thu Apr 25 2019
Journal Name
Journal Of Pharmacy Research
Pulsatile drug delivery system-review article
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Pulsatile drug delivery systems (PDDS) are developed to deliver drug according to circadian behavior of diseases. They deliver the drug at the right time, action and in the right amount, which provides more benefit than conventional dosages and increased patient compliance. The drug is released rapidly and completely as a pulse after a lag time. These systems are beneficial for drugs with chrono-pharmacological behavior, where nighttime dosing is required and for the drugs having a high first-pass effect and having specific site of absorption in the gastrointestinal tract. This article covers methods and marketed technologies that have been developed to achieve pulsatile delivery. Diseases wherein PDDS are promising include asthma, peptic u

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Publication Date
Sun Jun 24 2018
Journal Name
Journal Of Pharmacy Research
Transdermal drug delivery system: A review
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Transdermal drug delivery has made an important contribution to medical practice but has yet to fully achieve its potential as an alternative to oral delivery and hypodermic injections. Transdermal therapeutic systems have been designed to provide controlled continuous delivery of drugs through the skin to the systemic circulation. A transdermal patch is an adhesive patch that has a coating of drug; the patch is placed on the skin to deliver particular amount of drug into the systemic circulation over a period of time. The transdermal drug delivery systems (TDDS) review articles provide information regarding the transdermal drug delivery systems and its evaluation process as a ready reference for the research scientist who is involved

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Publication Date
Thu Nov 01 2018
Journal Name
Optical Fiber Technology
Enhancing refractive index sensitivity using micro-tapered long-period fiber grating inscribed in biconical tapered fiber
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Publication Date
Wed Apr 01 2020
Journal Name
Indian Journal Of Forensic Medicine & Toxicology
Hormonal and mineral imbalance effect on bone resorption in predialysis iraqi patients with chronic kidney disease
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Publication Date
Thu Dec 15 2022
Journal Name
Al-academy
The functional diversity of the directorial vision in the political theater cinema as a model
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It is very necessary for the political theater to be within the space of every theatrical performance, so that the theater carries the diverse and enlightened values and cultures of this world. political theatre. In the first chapter, the researcher dealt with (the methodological framework), which includes the research problem identified by the researcher with the following question (the functional diversity of the directorial vision in the political theater)
Importance, purpose, limits and seal by defining terminology.
In the second chapter, the researcher dealt with the theoretical framework on two topics, the first (transformations of directorial vision in theatrical performance) and the second topic (aesthetic experiences i

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