Publications by authors named "Nor Fazila Che Mat"

12 Publications

  • Page 1 of 1

Synergetic Influence of Bismuth Oxide Nanoparticles, Cisplatin and Baicalein-Rich Fraction on Reactive Oxygen Species Generation and Radiosensitization Effects for Clinical Radiotherapy Beams.

Int J Nanomedicine 2020 12;15:7805-7823. Epub 2020 Oct 12.

Medical Radiation Programme, School of Health Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan,Malaysia.

Purpose: This study aimed to quantify synergetic effects induced by bismuth oxide nanoparticles (BiONPs), cisplatin (Cis) and baicalein-rich fraction (BRF) natural-based agent on the reactive oxygen species (ROS) generation and radiosensitization effects under irradiation of clinical radiotherapy beams of photon, electron and HDR-brachytherapy. The combined therapeutic responses of each compound and clinical radiotherapy beam were evaluated on breast cancer and normal fibroblast cell line.

Methods: In this study, individual BiONPs, Cis, and BRF, as well as combinations of BiONPs-Cis (BC), BiONPs-BRF (BB) and BiONPs-Cis-BRF (BCB) were treated to the cells before irradiation using HDR brachytherapy with 0.38 MeV iridium-192 source, 6 MV photon beam and 6 MeV electron beam. The individual or synergetic effects from the application of the treatment components during the radiotherapy were elucidated by quantifying the ROS generation and radiosensitization effects on MCF-7 and MDA-MB-231 breast cancer cell lines as well as NIH/3T3 normal cell line.

Results: The ROS generated in the presence of Cis stimulated the most substantial amount of ROS compared to the BiONPs and BRF. Meanwhile, the combination of the components had induced the higher ROS levels for photon beam than the brachytherapy and electron beam. The highest ROS enhancement relative to the control is attributable to the presence of BC combination in MDA-MB-231 cells, in comparison to the BB and BCB combinations. The radiosensitization effects which were quantified using the sensitization enhancement ratio (SER) indicate the highest value by BC in MCF-7 cells, followed by BCB and BB treatment. The radiosensitization effects are found to be more prominent for brachytherapy in comparison to photon and electron beam.

Conclusion: The BiONPs, Cis and BRF are the potential radiosensitizers that could improve the efficiency of radiotherapy to eradicate the cancer cells. The combination of these potent radiosensitizers might produce multiple effects when applied in radiotherapy. The BC combination is found to have the highest SER, followed by the BCB combination. This study is also the first to investigate the effect of BRF in combination with BiONPs (BB) and BC (BCB) treatments.
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http://dx.doi.org/10.2147/IJN.S269214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7567565PMC
November 2020

Radiosensitization Effects by Bismuth Oxide Nanoparticles in Combination with Cisplatin for High Dose Rate Brachytherapy.

Int J Nanomedicine 2019 18;14:9941-9954. Epub 2019 Dec 18.

School of Health Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia.

Purpose: The aim of this study was to investigate the potential of the synergetic triple therapeutic combination encompassing bismuth oxide nanoparticles (BiONPs), cisplatin (Cis), and high dose rate (HDR) brachytherapy with Ir-192 source in breast cancer and normal fibroblast cell line.

Methods: In vitro models of breast cancer cell lines (MCF-7, MDA-MB-231) and normal fibroblast cell line (NIH/3T3) were employed. Cellular localization and cytotoxicity studies were conducted prior to inspection on the radiosensitization effects and generation of reactive oxygen species (ROS) on three proposed radiosensitizers: BiONPs, Cis, and BiONPs-Cis combination (BC). The optimal, non-cytotoxic concentration of BiONPs (0.5 mM) and the 25% inhibitory concentration of Cis (1.30 µM) were applied. The radiosensitization effects were evaluated by using a 0.38 MeV Iridium-192 HDR brachytherapy source over a prescribed dose range of 0 Gy to 4 Gy.

Results: The cellular localization of BiONPs was visualized by light microscopy and accumulation of the BiONPs within the vicinity of the nuclear membrane was observed. Quantification of the sensitization enhancement ratio extrapolated from the survival curves indicates radiosensitization effects for MCF-7 and MDA-MB-231 when treated with BiONPs, Cis, and BC. However, NIH/3T3 cells exhibited contradictive behavior as it only reacted towards the BC combination. Nonetheless, the MCF-7 cell line loaded with BC shows the highest SER of 4.29. ROS production analysis, on the other hand, shows that Cis and BC radiosensitizers generated the highest free radicals in comparison to BiONPs alone.

Conclusion: A BiONPs-Cis combination was unveiled as a novel approach that offers promising radiosensitization enhancement that will increase the efficiency of tumor control while preserving the normal tissue at a reduced dose. This data is the first precedent to prove the synergetic implication of BiONPs, Cis, and HDR brachytherapy that will be beneficial for future chemoradiotherapy strategies in cancer care.
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http://dx.doi.org/10.2147/IJN.S228919DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6927229PMC
April 2020

Population data of 23 Y chromosome STR loci for the five major human subpopulations of Ghana.

Int J Legal Med 2020 Jul 1;134(4):1313-1315. Epub 2019 Jun 1.

School of Health Sciences, Universiti Sains Malaysia, Health Campus, 16150, Kubang Kerian, Kelantan, Malaysia.

In this study, 268 samples for unrelated males belonging to the five major human subpopulation groups in Ghana (Akan, Ewe, Mole-Dagbon, Ga-Dangme and Guang) were genetically characterised for 23 Y chromosome short tandem repeat (STR) loci using the Powerplex® Y23 STR kit. A total of 263 complete haplotypes were recorded of which 258 were unique. The haplotype diversity, discriminating capacity and match probability for the pooled population data were 0.9998, 0.9627 and 0.0039, respectively. The pairwise genetic distance (R) for the Ghanaian datasets and other reference populations deposited in the Y-STR Haplotype Reference Database (YHRD) were estimated and mapped using multidimensional scaling (MDS) plot. The Guang and Ewe were significantly different from the Akan, Mole-Dagbon and Ga-Dangme. However, the five Ghanaian datasets were all plotted close together with other African populations in the MDS data mapping.
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http://dx.doi.org/10.1007/s00414-019-02099-wDOI Listing
July 2020

Transfusion Medicine and Molecular Genetic Methods.

Int J Prev Med 2018 16;9:45. Epub 2018 May 16.

School of Health Sciences, Health Campus, Universiti Sains Malaysia, Kelantan, Malaysia.

Transfusion procedures are always complicated by potential genetic mismatching between donor and recipient. Compatibility is determined by several major antigens, such as the ABO and Rhesus blood groups. Matching for other blood groups (Kell, Kidd, Duffy, and MNS), human platelet antigens, and human leukocyte antigens (HLAs) also contributes toward the successful transfusion outcomes, especially in multitransfused or highly immunized patients. All these antigens of tissue identity are highly polymorphic and thus present great challenges for finding suitable donors for transfusion patients. The ABO blood group and HLA markers are also the determinants of transplant compatibility, and mismatched antigens will cause graft rejection or graft-versus-host disease. Thus, a single and comprehensive registry covering all of the significant transfusion and transplantation antigens is expected to become an important tool in providing an efficient service capable of delivering safe blood and quickly locating matching organs/stem cells. This review article is intended as an accessible guide for physicians who care for transfusion-dependent patients. In particular, it serves to introduce the new molecular screening methods together with the biology of these systems, which underlies the tests.
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http://dx.doi.org/10.4103/ijpvm.IJPVM_232_16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5981227PMC
May 2018

Lymphocytic choriomeningitis virus infection of dendritic cells interferes with TLR-induced IL-12/IL-23 cytokine production in an IL-10 independent manner.

Cytokine 2018 08 27;108:105-114. Epub 2018 Mar 27.

Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Canada. Electronic address:

Dendritic cells produce IL-12 and IL-23 in response to viral and bacterial infection and these cytokines are responsible for successful pathogen clearance. How sequential viral and bacterial infections affect the production of IL-12 and IL-23 is currently not known. Our study demonstrates that in dendritic cells infected with Lymphocytic choriomeningitis virus (LCMV), TLR activation with bacterial PAMPs resulted in reduced IL-12 and IL-23 expression compared to non-infected cells. Furthermore, expression of other proinflammatory cytokines, TNF-α and IL-6, were not inhibited under these conditions. We discovered that TLR-induced phosphorylation of p38 was significantly inhibited in LCMV-infected cells. We detected enhanced expression of suppressor of cytokine signalling (SOCS)-3 and IL-10. Yet, neutralizing IL-10 did not restore IL-12/IL-23 expression. Taken together, these results show that virus infection interferes with the magnitude of TLR-mediated inflammatory responses by repressing specific cytokine expression.
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http://dx.doi.org/10.1016/j.cyto.2018.03.017DOI Listing
August 2018

Anti-viral Activities of Extracts on Chikungunya Virus Infection.

Indian J Microbiol 2018 Mar 28;58(1):68-75. Epub 2017 Nov 28.

1School of Health Sciences, Health Campus, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan Malaysia.

Chikungunya virus (CHIKV) is a re-emerging mosquito-borne alphavirus that poses a threat to human worldwide. Driven by the lack of approved medication and vaccination, research on anti-Chikungunya agents has received great attention. In an effort to determine potential inhibitor of CHIKV, this study aimed at investigating the potential anti-viral activity of extracts towards CHIKV-infected Vero cells. The virucidal, pre- and post-treatment effects of were evaluated, using the maximum non-toxic dose of methanol and aqueous extracts as determined by cytotoxicity assay. The viral inhibitory effect was assessed by the morphological changes of Vero cells and further confirmed by plaque assay. Both methanol and aqueous extracts of had similar cytotoxicity in Vero cells. Interestingly, the virucidal effect of aqueous extract revealed a significant reduction on the viral titre ( < 0.05). The prophylactic effect of aqueous extract was demonstrated when the pre-treated cells exhibited a significant anti-CHIKV activity ( < 0.05). However, methanol extract of this plant exerted an anti-viral activity against CHIKV only to a certain extent. Therefore, the aqueous extract of this plant has a potential to inhibit the virus and acts as prophylactic agent against CHIKV. Further studies however are needed to substantiate the finding and to determine the important compound of this plant as well as the mechanism of action in treating CHIKV infection.
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http://dx.doi.org/10.1007/s12088-017-0695-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5801184PMC
March 2018

IL-27-induced gene expression is downregulated in HIV-infected subjects.

PLoS One 2012 25;7(9):e45706. Epub 2012 Sep 25.

Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.

Objective: To characterize the effect of HIV infection on IL-27-induced gene expression.

Design: During HIV infection, cytokine expression and function become deregulated. IL-27 is an important modulator of inflammatory responses. Interestingly, IL-27 can inhibit HIV replication in T cells and monocytes, implicating IL-27 as a potential adjunct to anti-viral treatment. Our previous work demonstrated that circulating HIV may suppress IL-27 expression, therefore, this study, in continuation of our previous work, aimed to understand how HIV affects expression levels of the IL-27 receptor and downstream functions of IL-27.

Methods: Peripheral blood mononuclear cells (PBMC) were isolated from whole blood of HIV negative and HIV positive (viremic) individuals to assess IL-27-induced gene expression by flow cytometry and ELISA. PBMC were also processed for monocyte enrichment to assess IL-27 receptor expression by flow cytometry and real-time PCR.

Results: Expression of the IL-27 receptor subunit, gp130, was upregulated in response to IL-27 in HIV negative individuals, however, in HIV positive individuals, this IL-27 response was diminished. Furthermore, we observed downregulation of IL-27-induced IL-6, TNF-α, and IL-10 expression in HIV positive subjects.

Conclusion: In HIV infection, IL-27-induced gene expression was impaired, indicating HIV-mediated dysregulation of IL-27 functions occurs during HIV infection. This study provides evidence for new viral pathogenic mechanisms contributing to the widespread impairment of immune responses observed in HIV pathogenesis.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0045706PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3458084PMC
May 2013

Interleukin-23-induced interleukin-23 receptor subunit expression is mediated by the Janus kinase/signal transducer and activation of transcription pathway in human CD4 T cells.

J Interferon Cytokine Res 2011 Apr 7;31(4):363-71. Epub 2010 Dec 7.

Department of Microbiology and Immunology, Queen's University, Kingston, Ontario, Canada.

Interleukin (IL)-23 plays a critical role in the development of the T helper (Th) cell response and is responsible for the maintenance of the IL-17 producing subset of Th cells, Th17. IL-23 is a heterodimeric cytokine composed of IL-23p19 and IL-12p40 subunits, and the signaling pathway for IL-23 involves 2 receptor chains: IL-12Rβ1 and IL-23Rα. The IL-23 receptor complex is expressed on a number of cells, including natural killer cells, monocytes, macrophages, dendritic cells, and CD4 T cells. Currently, the molecular mechanisms governing expression of the IL-23 receptor chains, IL-23Rα and IL-12Rβ1, are not well understood. Our results show that IL-23 induces upregulation of IL-23Rα and IL-12Rβ1 expression in human CD4 T cells. Further, we demonstrate that inhibition of the Janus kinase/signal transducer and activation of transcription (JAK/STAT) pathway by SD-1029, a JAK2 inhibitor, 5'-deoxy-5'-(methylthio) adenosine, a STAT1 inhibitor, and STAT3 VII, a STAT3 inhibitor, were able to block IL-23-induced expression of IL-23 receptor subunits in the human SUPT-1 T cell line and in primary CD4 human T cells. Taken together, our results suggest a positive feedback regulation of the IL-23 receptor via IL-23-mediated activation of the JAK/STAT pathway.
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http://dx.doi.org/10.1089/jir.2010.0083DOI Listing
April 2011

Interleukin-27 induces a STAT1/3- and NF-kappaB-dependent proinflammatory cytokine profile in human monocytes.

J Biol Chem 2010 Aug 2;285(32):24404-11. Epub 2010 Jun 2.

Department of Microbiology and Immunology, Queen's University, Kingston, Ontario K7L 3N6, Canada.

IL-27 is a heterodimeric cytokine bridging innate and adaptive immunity by playing a role in the activation of naive T cells and in development of Th1 cells. Additionally, recent evidence supports a role for IL-27 in the activation of monocytic cells. Both pro-inflammatory and anti-inflammatory activities have been attributed to IL-27; however, the role played by IL-27 in the activation of human monocytic cells in terms of cytokine production has not been well described. Our results show that IL-27 is a strong inducer of proinflammatory cytokine and chemokine expression, including enhancement of IL-6, IP-10, MIP-1alpha, MIP-1beta, and TNF-alpha expression in human primary monocytes. Furthermore, we observed that IL-27-induced cytokine and chemokine production was mediated by STAT1, STAT3, and NF-kappaB activation. Understanding how IL-27 exerts its effects on monocytic cells will identify important molecular mechanisms in the regulation of immune responses, particularly in the modulation of monocyte activation.
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http://dx.doi.org/10.1074/jbc.M110.112599DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2915676PMC
August 2010

Impact of HIV infection, highly active antiretroviral therapy, and hepatitis C coinfection on serum interleukin-27.

AIDS 2010 Jun;24(9):1371-4

Department of Microbiology and Immunology, Queen's University, Kingston, Ontario, Canada.

A newly described cytokine, interleukin-27 (IL-27), that activates naive CD4 T cells, has recently been shown to be an anti-HIV cytokine. However, the effect of HIV infection on IL-27 expression has not been characterized. We found that clinical characteristics, including HIV viral load, hepatitis C virus coinfection, and CD4 T cell counts, were associated with changes in serum IL-27. Overall, our results suggest circulating HIV may suppress IL-27, a critical concept in treatment development with this cytokine.
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http://dx.doi.org/10.1097/QAD.0b013e3283391d2bDOI Listing
June 2010

The IL-12 family of cytokines in infection, inflammation and autoimmune disorders.

Inflamm Allergy Drug Targets 2009 Mar;8(1):40-52

Department of Microbiology and Immunology, Queen's University, Kingston ON, Canada.

Cytokines are critical coordinators of the immune response necessary for resolving bacterial and viral assaults on the immune system. In particular, the IL-12 family of cytokines are key players in the regulation of T cell responses. These responses are orchestrated by monocytes, macrophages, and dendritic cells which produce the members of the IL-12 family of cytokines in response to infection. IL-27 and IL-23 are two cytokines that are related to IL-12; these cytokines share homology at the subunit, receptor, and signalling levels. IL-12 is composed of p35 and p40 subunits, which, when combined together form the bioactive IL-12p70. IL-23 is composed of the IL-12p40 subunit as well as the IL-23p19 subunit, which shares homology with IL-12p35. IL-27 is composed of EBI3 and p28. These three cytokines activate similar members of the JAK/STAT signalling pathways as a result of homology in their receptor components. Production of these cytokines by activated monocytes, macrophages, and dendritic cells results in the activation and differentiation of T cells. In spite of their similarity, each of these cytokines has specific roles in the regulation of immune responses. IL-12 is required for the induction of IFN-gamma production, critical for the induction of Th1 cells. IL-27 has been shown to play a role in the induction of Th1 cells from naive T cells, whereas IL-23 has been demonstrated to play a key role in the induction of the newly described Th17 cells. Recently, a novel heterodimeric and anti-inflammatory cytokine composed of the IL-12p35 and EBI3 subunits has been identified as IL-35. The biological properties of the IL-12 family of cytokines, the signalling pathways mediated by these cytokines and their role in infection, inflammation, and autoimmune diseases will be the focus of this review.
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http://dx.doi.org/10.2174/187152809787582507DOI Listing
March 2009
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