Publications by authors named "Abdul Rahim Hussein"

7 Publications

  • Page 1 of 1

Transcriptomic Profiles of MV4-11 and Kasumi 1 Acute Myeloid Leukemia Cell Lines Modulated by Epigenetic Modifiers Trichostatin A and 5-Azacytidine.

Int J Hematol Oncol Stem Cell Res 2020 Jan;14(1):72-92

Department of Hematology, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia.

Acute myeloid leukemia (AML) is the most common form of acute leukemias in adults which is clinically and molecularly heterogeneous. Several risk and genetic factors have been widely investigated to characterize AML. However, the concomitant epigenetic factors in controlling the gene expression lead to AML transformation was not fully understood. This study was aimed to identify epigenetically regulated genes in AML cell lines induced by epigenetic modulating agents, Trichostatin A (TSA) and 5-Azacytidine (5-Aza). MV4-11 and Kasumi 1 were treated with TSA and/or 5-Aza at IC concentration. Gene expression profiling by microarray was utilized using SurePrint G3 Human Gene Expression v3. Gene ontology and KEGG pathway annotations were analyzed by DAVID bioinformatics software using EASE enrichment score. mRNA expression of the differentially expressed genes were verified by quantitative real time PCR. Gene expression analysis revealed a significant changes in the expression of 24,822, 15,720, 15,654 genes in MV4-11 and 12,598, 8828, 18,026 genes in Kasumi 1, in response to TSA, 5-Aza and combination treatments, respectively, compared to non-treated (<0.05). 7 genes (, , , , , and ) and 4 genes (, , and ) shown to be predominantly expressed in MV4-11 and Kasumi 1, respectively (EASE<0.1). The analysis also revealed phagosome pathway commonly activated in both cell lines. Our data showed a distinct optimal biological characteristic and pathway in different types of leukemic cell lines. These finding may help in the identification of cell-specific epigenetic biomarker in the pathogenesis of AML.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7167603PMC
January 2020

Coagulation Factor Activities Changes Over 5 Days in Thawed Fresh Frozen Plasma Stored at Different Initial Storage Temperatures.

Indian J Hematol Blood Transfus 2018 Jul 7;34(3):510-516. Epub 2017 Oct 7.

4Regenerative Medicine Cluster, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Bertam, 13200 Penang, Kepala Batas Malaysia.

Thawed plasma is fresh frozen plasma (FFP) that has been stored for 5 days at 1-6 °C. Duration of storage and different storage temperatures might affect the coagulation factor activity in thawed FFP. This study measured the changes of coagulation factor activities over 5 days in thawed FFP and stored at two different initial storage temperatures. Thirty-six units of FFP, which consisted of nine units each from blood groups A, B, AB, and O, were thawed at 37 °C. Each unit was divided into two separate groups (Group A and Group B) based on initial storage temperature. The first group was stored at 2-6 °C for 5 days (Group A). The second group was stored at 20-24 °C for initial 6 h followed by 2-6 °C for 5 days (Group B). Prothrombin time (PT), activated partial thromboplastin time (APTT), coagulation factor activities of fibrinogen, factor (F) II, FV, FVII, FVIII, FIX, FX, and von Willebrand factor antigen (vWF Ag) were assessed at baseline after thawing, at 6 h, and on days 1, 3, and 5 of storage for both groups. All coagulation factors mean activities in both storage groups decreased significantly over 5 days of storage. The mean FVIII activity at day 5 of storage was 36.9% in Group A and 39.8% in Group B. The other coagulation factors mean activities were > 50% on day 5 of storage in both groups. The coagulation factor activities of thawed FFP stored for 5 consecutive days were reduced in the two storage groups but most of the activities were still above 30%. This study suggests that thawed FFP stored for 5 days has the potential to ameliorate coagulation factor deficiencies in affected patients.
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http://dx.doi.org/10.1007/s12288-017-0879-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6081346PMC
July 2018

Chitosan scaffold enhances growth factor release in wound healing in von Willebrand disease.

Int J Clin Exp Med 2015 15;8(9):15611-20. Epub 2015 Sep 15.

Industrial Biotechnology Research Centre, SIRIM Berhad No. 1 Persiaran Dato' Menteri, Section 2, P. O. Box 7035, Shah Alam 40700, Selangor, Malaysia.

Chitosan-derived biomaterials have been reported to adhere when in contact with blood by encouraging platelets to adhere, activate and aggregate at the sites of vascular injury, thus enhanced wound healing capacity. This study investigated platelet morphology changes and the expression level of transforming growth factor-β1 (TGF-β1) and platelet-derived growth factor-AB (PDGF-AB) in the adherence of two different types of chitosans in von Willebrand disease (vWD): N,O-carboxymethylchitosan (NO-CMC) and oligo-chitosan (O-C). Fourteen vWD voluntary subjects were recruited, and they provided written informed consent. Scanning electron microscopy and enzyme-linked immunosorbent assay test procedures were employed to achieve the objective of the study. The results suggest that the O-C group showed dramatic changes in the platelet's behaviors. Platelets extended filopodia and generated lamellipodia, leading to the formation of grape-like shaped aggregation. The platelet aggregation occurred depending on the severity of vWD. O-C was bound to platelets on approximately 90% of the surface membrane in vWD type 1; there was 70% and 50% coverage in vWD type II and III, respectively. The O-C chitosan group showed an elevated expression level of TGF-β1 and PDGF-AB. This finding suggests that O-C stimulates these mediators from the activated platelets to the early stage of restoring the damaged cells and tissues. This study demonstrated that the greater expression level of O-C assists in mediating the cytokine complex networks of TGF-β1 and PDGF-AB and induces platelet activities towards wound healing in vWD. With a better understanding of chitosan's mechanisms of action, researchers are able to accurately develop novel therapies to prevent hemorrhage.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4658944PMC
December 2015

Effect of the Novel Biodegradable N, O-Carboxymethylchitosan and Oligo-Chitosan on the Platelet Thrombogenicity Cascade in von Willebrand Disease.

Thromb Res 2015 Sep 30;136(3):625-33. Epub 2015 Jul 30.

Industrial Biotechnology Research Centre, SIRIM Berhad, No. 1 Persiaran Dato' Menteri, Section 2, P.O. Box 7035, 40700 Shah Alam, Selangor, Malaysia. Electronic address:

Introduction: Von Willebrand disease (vWD) is the second least common hemostatic disorder in Malaysia, and it has a low prevalence. This study examined the underlying platelet thrombogenicity cascades in the presence of different formulations of chitosan-derivatives in vWD patients. This paper aimed to determine the significant influence of chitosan biomaterial in stimulating the platelet thrombogenicity cascades that involve the von Willebrand factor, Factor 8, Thromboxane A2, P2Y12 and Glycoprotein IIb/IIIa in vWD.

Materials And Methods: Variable chitosan formulations of N,O-Carboxymethylchitosan (NO-CMC) and Oligo-Chitosan (O-C) were tested. Fourteen vWD subjects voluntarily participated in this study after signing informed consent forms. The patient's demographic profiles, family history, type of vWD, clinical symptoms and laboratory profiles were recorded and analyzed. Enzyme-linked immunosorbent assay, flow cytometry and Western blot tests were used to determine the level of the chitosan-adhered-platelet-mechanisms.

Results: The study revealed that most patients were predominantly affected by vWD type I. The O-C group of chitosan's scaffold pores is sufficient to allow for nutrients and cells. The O-C-stimulated-mediators are capable of initiating the platelet actions and were detected to expedite the blood coagulation processes. The oligo-group of chitosans was capable of amplifying and triggering more platelet activator's pathways via the studied mediators. The present findings suggest that the ability of each type of chitosan to coagulate blood varies depending on its chemical composition.

Conclusion: The oligo group of chitosans is potentially capable of triggering platelet thrombogenicity cascades by activating platelets in vWD patients to form a platelet plug for hemostasis process.
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http://dx.doi.org/10.1016/j.thromres.2015.07.027DOI Listing
September 2015

Characterisation and Clinical Significance of FLT3-ITD and non-ITD in Acute Myeloid Leukaemia Patients in Kelantan, Northeast Peninsular Malaysia.

Asian Pac J Cancer Prev 2015 ;16(12):4869-72

Department of Hematology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia E-mail :

Background: Mutations of the FMS-like tyrosine kinase-3 (FLT3) receptor gene may promote proliferation via activation of multiple signaling pathways. FLT3-internal tandem duplication (FLT3-ITD) is the most common gene alteration found in patients diagnosed with acute myeloid leukaemia (AML) and has been associated with poor prognosis.

Materials And Methods: We performed mutational analysis of exons 14-15 and 20 of the FLT3 gene in 54 AML patients using PCR-CSGE (conformational sensitive gel electrophoresis) followed by sequencing analysis to characterise FLT3 mutations in adult patients diagnosed with AML at Hospital USM, Kelantan, Northeast Peninsular Malaysia.

Results: FLT3 exon 14-15 mutations were identified in 7 of 54 patients (13%) whereas no mutation was found in FLT3 exon 20. Six ITDs and one non-ITD mutation were found in exon 14 of the juxtamembrane (JM) domain of FLT3. FLT3-ITD mutations were associated with a significantly higher blast percentage (p-value=0.008) and white blood cell count (p-value=0.023) but there was no significant difference in median overall survival time for FLT3-ITD+/FLT3-ITD- within 2 years (p-value=0.374).

Conclusions: The incidence of FLT3-ITD in AML patients in this particular region of Malaysia is low compared to the Western world and has a significant association with WBC and blast percentage.
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http://dx.doi.org/10.7314/apjcp.2015.16.12.4869DOI Listing
April 2016

Glycoprotein IIb/IIIa and P2Y12 induction by oligochitosan accelerates platelet aggregation.

Biomed Res Int 2014 28;2014:653149. Epub 2014 Aug 28.

Industrial Biotechnology Research Centre, SIRIM Berhad, No. 1 Persiaran Dato' Menteri, Section 2, P.O. Box 7035, 40700 Shah Alam, Selangor, Malaysia.

Platelet membrane receptor glycoprotein IIb/IIIa (gpiibiiia) is a receptor detected on platelets. Adenosine diphosphate (ADP) activates gpiibiiia and P2Y12, causing platelet aggregation and thrombus stabilization during blood loss. Chitosan biomaterials were found to promote surface induced hemostasis and were capable of activating blood coagulation cascades by enhancing platelet aggregation. Our current findings show that the activation of the gpiibiiia complex and the major ADP receptor P2Y12 is required for platelet aggregation to reach hemostasis following the adherence of various concentrations of chitosan biomaterials [7% N,O-carboxymethylchitosan (NO-CMC) with 0.45 mL collagen, 8% NO-CMC, oligochitosan (O-C), and oligochitosan 53 (O-C 53)]. We studied gpiibiiia and P2Y12 through flow cytometric analysis and western blotting techniques. The highest expression of gpiibiiia was observed with Lyostypt (74.3 ± 7.82%), followed by O-C (65.5 ± 7.17%). Lyostypt and O-C resulted in gpiibiiia expression increases of 29.2% and 13.9%, respectively, compared with blood alone. Western blot analysis revealed that only O-C 53 upregulated the expression of P2Y12 (1.12 ± 0.03-fold) compared with blood alone. Our findings suggest that the regulation of gpiibiiia and P2Y12 levels could be clinically useful to activate platelets to reach hemostasis. Further, we show that the novel oligochitosan is able to induce the increased expression of gpiibiiia and P2Y12, thus accelerating platelet aggregation in vitro.
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http://dx.doi.org/10.1155/2014/653149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4163351PMC
June 2015

In vitro capacity of different grades of chitosan derivatives to induce platelet adhesion and aggregation.

Int J Biol Macromol 2013 Jan 11;52:244-9. Epub 2012 Oct 11.

Reconstructive Sciences Unit, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia.

Chitosan-derived hemostatic agents with various formulations may have distinct potential in hemostasis. This study assessed the ability of different grades and forms of chitosan derivatives as hemostatic agents to enhance platelet adhesion and aggregation in vitro. The chitosan derivatives utilized were 2% NO-CMC, 7% NO-CMC (with 0.45 mL collagen), 8% NO-CMC, O-C 52, 5% O-CMC-47, NO-CMC-35, and O-C 53. Samples of chitosan derivatives weighing 5mg were incubated at 37°C with 50 μL of phosphate buffer saline (PBS) (pH 7.4) for 60 min. The morphological features of the platelets upon adherence to the chitosan were viewed using scanning electron microscope (SEM), and the platelet count was analyzed with an Automated Hematology Analyzer. For platelet aggregation, we added an adenosine diphosphate (ADP) agonist to induce the chitosan-adhered platelets. O-C 52 bound with platelets exhibited platelet aggregates and clumps on the surface of the membrane layer with approximately 70-80% coverage. A statistically significant correlation (p<0.01) for the platelet count was identified between the baseline value and the values at 10 min and 20 min. The results indicate that O-C 53 and O-C 52 were able to promote clotting have the potential to induce the release of platelets engaged in the process of hemostasis.
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http://dx.doi.org/10.1016/j.ijbiomac.2012.10.001DOI Listing
January 2013