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  1. Abdullah MA, Albarody TMB, Hussein AR
    Nanotechnology, 2020 Apr 24;31(28):285709.
    PMID: 32176874 DOI: 10.1088/1361-6528/ab8040
    Precision temperature measurement of a nano system with high sensitivity and fast response is still a challenge. The marvelous thermal and mechanical properties of graphite will allow the creation of superior nanoscale temperature sensors. In-situ x-ray diffraction was employed to determine the graphite hexagonal crystal lattice dimensions and the coefficient of thermal expansion based on the calculation of its interatomic distance. The energy of graphite was mapped over the first Brillouin zone in the temperature range of 50 °C-1200 °C at intervals of 50 °C. Energy-based comparative studies between the quantum free electron approach obtained by an inelastic scattering and an harmonic oscillator are introduced by the principal quantum number associated with the excitation level. The hexagonal lattice constants, interlayer distance and interatomic distance of graphite crystals are investigated analytically with consideration given to their temperature dependence and the carbon peak (002), where the 2θ value decreases slightly with increasing temperature. The coefficient of thermal expansion of graphite-based interatomic distance is negative and tends toward zero with increasing temperature, which is in very good agreement with experiments. Moreover, the energy probability distributions enclosed by reciprocal lattice vectors of the hexagonal lattice are defined and interpreted based on lattice dimensions with varying temperature. Linear changes of the temperature-driven unit cell lattice dimensions and analysis of the kinetic energy of the electron in graphite may both be utilised for the advanced temperature interpretation model and preliminary design of a precise nanothermometer.
  2. Periayah MH, Halim AS, Hussein AR, Saad AZ, Rashid AH, Noorsal K
    Int J Biol Macromol, 2013 Jan;52:244-9.
    PMID: 23063426 DOI: 10.1016/j.ijbiomac.2012.10.001
    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.
  3. Yunus NM, Johan MF, Ali Nagi Al-Jamal H, Husin A, Hussein AR, Hassan R
    Asian Pac J Cancer Prev, 2015;16(12):4869-72.
    PMID: 26163606
    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.

  4. Noordin SS, Karim FA, Mohammad WMZBW, Hussein AR
    Indian J Hematol Blood Transfus, 2018 Jul;34(3):510-516.
    PMID: 30127563 DOI: 10.1007/s12288-017-0879-8
    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.
  5. Mazlan AM, Ayob Y, Hussein AR, Namasiwayam TK, Wan Mohammad WMZ
    Asian J Transfus Sci, 2017 Jul-Dec;11(2):95-101.
    PMID: 28970674 DOI: 10.4103/ajts.AJTS_51_16
    CONTEXT: Coronary artery bypass graft (CABG) operation is associated with high frequency of allogeneic blood transfusion due to the acquired hemostatic challenges in patients undergoing CABG. However, allogeneic blood transfusion carries risks of infection, adverse reaction, and mortality as well as prolonged hospital stay and increased hospital cost. It is important to identify patients who require blood transfusion to mitigate their risk factors and reduce the chance of exposure to allogeneic blood.

    AIMS: This study was conducted to evaluate factors that influence the decision to transfuse red cell in first-time elective CABG patients.

    SETTINGS AND DESIGN: This was a cross-sectional study based on a retrospective record review. The study was done in the National Heart Institute.

    MATERIALS AND METHODS: All patients who underwent first-time elective CABG were included in this study. Variables analyzed include age, gender, body weight, preoperative hemoglobin (Hb) level, patients' comorbidities, and other clinical parameters.

    STATISTICAL ANALYSIS USED: Data were analyzed using SPSS software version 20.

    RESULTS: A total of 463 patients underwent first-time elective CABG during the period of the study. Three hundred and eighty-six (83.4%) patients received red cell transfusion. From multiple logistic regression analysis, only age (odds ratio [OR] = 1.040, 95% confidence interval [CI]: 1.003, 1.077, P = 0.032), body weight (OR = 0.951, 95% CI: 0.928, 0.974, P < 0.001), Hb level (OR = 0.500, 95% CI: 0.387, 0.644, P < 0.001), and cardiopulmonary bypass time (OR = 1.013, 95% CI: 1.004, 1.023, P < 0.001) were the significant independent predictors of red cell transfusion.

    CONCLUSIONS: By stratifying patients according to their risk factor for red cell transfusion, the high-risk patients could be recognized and should be enrolled into effective patient blood management program to minimize their risk of exposure to allogeneic blood transfusion.
  6. Periayah MH, Halim AS, Yaacob NS, Saad AZ, Hussein AR, Rashid AH, et al.
    Biomed Res Int, 2014;2014:653149.
    PMID: 25247182 DOI: 10.1155/2014/653149
    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.
  7. Periayah MH, Halim AS, Mat Saad AZ, Yaacob NS, Hussein AR, Abdul Karim F, et al.
    Thromb Res, 2015 Sep;136(3):625-33.
    PMID: 26254703 DOI: 10.1016/j.thromres.2015.07.027
    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.
  8. Asmaa MJS, Al-Jamal HA, Hussein AR, Yahaya BH, Hassan R, Hussain FA, et al.
    Int J Hematol Oncol Stem Cell Res, 2020 Jan 01;14(1):72-92.
    PMID: 32337016
    Background: 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). Materials and Methods: MV4-11 and Kasumi 1 were treated with TSA and/or 5-Aza at IC50 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. Results: 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 (p<0.05). 7 genes (SOCS3, TUBA1C, CCNA1, MAP3K6, PTPRC, STAT6 and RUNX1) and 4 genes (ANGPTL4, TUBB2A, ADAM12 and PTPN6) 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. Conclusion: 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.
  9. Periayah MH, Halim AS, Saad AZ, Yaacob NS, Hussein AR, Karim FA, et al.
    Int J Clin Exp Med, 2015;8(9):15611-20.
    PMID: 26629055
    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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