Displaying publications 21 - 40 of 74 in total

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  1. Rahman MT, Haque N, Abu Kasim NH, De Ley M
    PMID: 28417197 DOI: 10.1007/112_2017_1
    Toxic heavy metals, toxic organic compounds, reactive oxygen species (ROS), infections, and temperature are well-known metallothionein (MT) inducers in human blood. The current review aims to summarize synthesis, function, and fate of human blood MT in response to the known MT inducers. Part of the MTs that are synthesized in different organs such as the liver, kidney, and spleen is transported and stored in different blood cells and in plasma. Cells of the circulatory system also synthesize MT. From the circulation, MT returns to the kidney where the metal-bound MTs are degraded to release the metal ion that in turn induces MT expression therein. The blood MTs play important roles in metal detoxification, transportation, and storage. By neutralizing ROS, MTs protect blood cells from oxidative stress-induced cytotoxicity and genotoxicity. Arguably, MTs are also involved in immune suppression. Given the permeating distribution of blood MT throughout the body as well as its diverse role in the protection against harmful environmental factors and in metal homeostasis, MT could be better recognized as a major public health protein.
  2. Gnanasegaran N, Govindasamy V, Mani V, Abu Kasim NH
    IUBMB Life, 2017 09;69(9):689-699.
    PMID: 28685937 DOI: 10.1002/iub.1655
    In neurodegenerative diseases, such as Alzheimer's and Parkinson's, microglial cell activation is thought to contribute to their degeneration by producing neurotoxic compounds. While dental pulp stem cells (DPSCs) have been regarded as the next possible cell source for cell replacement therapy (CRT), their actual role when exposed in such harsh environment remains elusive. In this study, the immunomodulatory behavior of DPSCs from human subjects was investigated in a coculture system consisting of neuron and microglia which were treated with 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine, which mimics the inflammatory conditions and contribute to degeneration of dopaminergic (DA-ergic) neurons. Assessments were performed on their proliferation, extent of DNA damage, productions of reactive oxygen species (ROS) and nitric oxide (NO), as well as secretion of inflammatory mediators. Notably, DPSCs were shown to attenuate their proliferation, production of ROS, and NO significantly (P 
  3. Gnanasegaran N, Govindasamy V, Kathirvaloo P, Musa S, Abu Kasim NH
    J Tissue Eng Regen Med, 2018 02;12(2):e881-e893.
    PMID: 28079995 DOI: 10.1002/term.2401
    Parkinson's disease (PD) is characterized by tremors and cognitive issues, and is due to the death of dopaminergic (DA-ergic) neurons in brain circuits that are responsible for producing neurotransmitter dopamine (DA). Currently, cell replacement therapies are underway to improve upon existing therapeutic approaches such as drug treatments and electrical stimulation. Among the widely available sources, dental pulp stem cells (DPSCs) from deciduous teeth have gained popularity because of their neural crest origin and inherent propensity toward neuronal lineage. Despite the various pre-clinical studies conducted, an important factor yet to be elucidated is the influence of growth phases in a typical trans-differentiation process. This study selected DPSCs at three distinct time points with variable growth phase proportions (G0/G1, S and G2/M) for in vitro trans-differentiation into DA-ergic-like cells. Using commercially available PCR arrays, we identified distinct gene profiles pertaining to cell cycles in these phases. The differentiation outcomes were assessed in terms of morphology and gene and protein expression, as well as with functional assays. It was noted that DPSCs with the highest G0/G1 phase were comparatively the best, representing at least a 2-fold up regulation (p 
  4. Haque N, Widera D, Govindasamy V, Soesilawati P, Abu Kasim NH
    Curr Mol Med, 2022;22(2):120-131.
    PMID: 33550972 DOI: 10.2174/1566524021666210125114828
    Cell-based regenerative therapies involving stem or progenitor cells are considered as possible therapeutic modalities to treat non-communicable and degenerative diseases. Recently, regenerative outcomes of cell-based therapies have been linked to paracrine factors and extracellular vesicles [EVs] released by the transplanted cells rather than the transplanted cells themselves. EVs contain a cargo that includes microRNAs [miRNAs], mRNAs, as well as proteins. Their role in mediating intercellular communication has been acknowledged in several studies. However, the regenerative potential of the miRNAs, mRNAs, and proteins that are present in EVs is a matter of ongoing scientific debate. In this review, we discuss EVs as an alternative to stem cell-based therapy to treat some of the non-communicable and degenerative diseases. Moreover, we also propose that pre-treatment of the cells could help to produce EVs enriched with particular miRNAs, mRNAs, and/or proteins that could support the successful regeneration of a targeted organ.
  5. Srijaya TC, Ramasamy TS, Kasim NH
    J Transl Med, 2014;12:243.
    PMID: 25182194 DOI: 10.1186/s12967-014-0243-9
    The inadequacy of existing therapeutic tools together with the paucity of organ donors have always led medical researchers to innovate the current treatment methods or to discover new ways to cure disease. Emergence of cell-based therapies has provided a new framework through which it has given the human world a new hope. Though relatively a new concept, the pace of advancement clearly reveals the significant role that stem cells will ultimately play in the near future. However, there are numerous uncertainties that are prevailing against the present setting of clinical trials related to stem cells: like the best route of cell administration, appropriate dosage, duration and several other applications. A better knowledge of these factors can substantially improve the effectiveness of disease cure or organ repair using this latest therapeutic tool. From a certain perspective, it could be argued that by considering certain proven clinical concepts and experience from synthetic drug system, we could improve the overall efficacy of cell-based therapies. In the past, studies on synthetic drug therapies and their clinical trials have shown that all the aforementioned factors have critical ascendancy over its therapeutic outcomes. Therefore, based on the knowledge gained from synthetic drug delivery systems, we hypothesize that by employing many of the clinical approaches from synthetic drug therapies to this new regenerative therapeutic tool, the efficacy of stem cell-based therapies can also be improved.
  6. Mohd N, Razali M, Fauzi MB, Abu Kasim NH
    Int J Mol Sci, 2023 Aug 17;24(16).
    PMID: 37629064 DOI: 10.3390/ijms241612881
    Three-dimensional (3D) bioprinting is a unique combination of technological advances in 3D printing and tissue engineering. It has emerged as a promising approach to address the dilemma in current dental treatments faced by clinicians in order to repair or replace injured and diseased tissues. The exploration of 3D bioprinting technology provides high reproducibility and precise control of the bioink containing the desired cells and biomaterial over the architectural and dimensional features of the scaffolds in fabricating functional tissue constructs that are specific to the patient treatment need. In recent years, the dental applications of different 3D bioprinting techniques, types of novel bioinks, and the types of cells used have been extensively explored. Most of the findings noted significant challenges compared to the non-biological 3D printing approach in constructing the bioscaffolds that mimic native tissues. Hence, this review focuses solely on the implementation of 3D bioprinting techniques and strategies based on cell-laden bioinks. It discusses the in vitro applications of 3D-bioprinted scaffolds on cell viabilities, cell functionalities, differentiation ability, and expression of the markers as well as the in vivo evaluations of the implanted bioscaffolds on the animal models for bone, periodontal, dentin, and pulp tissue regeneration. Finally, it outlines some perspectives for future developments in dental applications.
  7. Mohd N, Razali M, Ghazali MJ, Abu Kasim NH
    Materials (Basel), 2022 Sep 15;15(18).
    PMID: 36143709 DOI: 10.3390/ma15186398
    Three-dimensional (3D) bioprinting technology has emerged as an ideal approach to address the challenges in regenerative dentistry by fabricating 3D tissue constructs with customized complex architecture. The dilemma with current dental treatments has led to the exploration of this technology in restoring and maintaining the function of teeth. This scoping review aims to explore 3D bioprinting technology together with the type of biomaterials and cells used for dental applications. Based on PRISMA-ScR guidelines, this systematic search was conducted by using the following databases: Ovid, PubMed, EBSCOhost and Web of Science. The inclusion criteria were (i) cell-laden 3D-bioprinted construct; (ii) intervention to regenerate dental tissue using bioink, which incorporates living cells or in combination with biomaterial; and (iii) 3D bioprinting for dental applications. A total of 31 studies were included in this review. The main 3D bioprinting technique was extrusion-based approach. Novel bioinks in use consist of different types of natural and synthetic polymers, decellularized extracellular matrix and spheroids with encapsulated mesenchymal stem cells, and have shown promising results for periodontal ligament, dentin, dental pulp and bone regeneration application. However, 3D bioprinting in dental applications, regrettably, is not yet close to being a clinical reality. Therefore, further research in fabricating ideal bioinks with implantation into larger animal models in the oral environment is very much needed for clinical translation.
  8. Mohd N, Razali M, Ghazali MJ, Abu Kasim NH
    Materials (Basel), 2022 Apr 02;15(7).
    PMID: 35407950 DOI: 10.3390/ma15072621
    Three-dimensional-printed scaffolds have received greater attention as an attractive option compared to the conventional bone grafts for regeneration of alveolar bone defects. Hydroxyapatite and tricalcium phosphates have been used as biomaterials in the fabrication of 3D-printed scaffolds. This scoping review aimed to evaluate the potential of 3D-printed HA and calcium phosphates-based scaffolds on alveolar bone regeneration in animal models. The systematic search was conducted across four electronic databases: Ovid, Web of Science, PubMed and EBSCOHOST, based on PRISMA-ScR guidelines until November 2021. The inclusion criteria were: (i) animal models undergoing alveolar bone regenerative surgery, (ii) the intervention to regenerate or augment bone using 3D-printed hydroxyapatite or other calcium phosphate scaffolds and (iii) histological and microcomputed tomographic analyses of new bone formation and biological properties of 3D-printed hydroxyapatite or calcium phosphates. A total of ten studies were included in the review. All the studies showed promising results on new bone formation without any inflammatory reactions, regardless of the animal species. In conclusion, hydroxyapatite and tricalcium phosphates are feasible materials for 3D-printed scaffolds for alveolar bone regeneration and demonstrated bone regenerative potential in the oral cavity. However, further research is warranted to determine the scaffold material which mimics the gold standard of care for bone regeneration in the load-bearing areas, including the masticatory load of the oral cavity.
  9. Dabbagh A, Mahmoodian R, Abdullah BJ, Abdullah H, Hamdi M, Abu Kasim NH
    Int J Hyperthermia, 2015;31(8):920-9.
    PMID: 26670340 DOI: 10.3109/02656736.2015.1094147
    The aim of this paper was to synthesise core-shell nanostructures comprised of mesoporous silica core and a low melting-point polyethylene glycol (PEG) nanoshell with a sharp gel-liquid phase transition for rapid drug release at hyperthermia temperature range.
  10. Dabbagh A, Abdullah BJ, Abu Kasim NH, Abdullah H, Hamdi M
    Int J Hyperthermia, 2015 Jun;31(4):375-85.
    PMID: 25716769 DOI: 10.3109/02656736.2015.1006268
    The aim of this paper was to introduce a new mechanism of thermal sensitivity in nanocarriers that results in a relatively low drug release at physiological temperature and rapid release of the encapsulated drug at hyperthermia and thermal ablation temperature range (40-60 °C).
  11. Loo ZX, Kunasekaran W, Govindasamy V, Musa S, Abu Kasim NH
    ScientificWorldJournal, 2014;2014:186508.
    PMID: 25548778 DOI: 10.1155/2014/186508
    Human exfoliated deciduous teeth (SHED) and adipose stem cells (ASC) were suggested as alternative cell choice for cardiac regeneration. However, the true functionability of these cells toward cardiac regeneration is yet to be discovered. Hence, this study was carried out to investigate the innate biological properties of these cell sources toward cardiac regeneration. Both cells exhibited indistinguishable MSCs characteristics. Human stem cell transcription factor arrays were used to screen expression levels in SHED and ASC. Upregulated expression of transcription factor (TF) genes was detected in both sources. An almost equal percentage of >2-fold changes were observed. These TF genes fall under several cardiovascular categories with higher expressions which were observed in growth and development of blood vessel, angiogenesis, and vasculogenesis categories. Further induction into cardiomyocyte revealed ASC to express more significantly cardiomyocyte specific markers compared to SHED during the differentiation course evidenced by morphology and gene expression profile. Despite this, spontaneous cellular beating was not detected in both cell lines. Taken together, our data suggest that despite being defined as MSCs, both ASC and SHED behave differently when they were cultured in a same cardiomyocytes culture condition. Hence, vigorous characterization is needed before introducing any cell for treating targeted diseases.
  12. Vasanthan P, Govindasamy V, Gnanasegaran N, Kunasekaran W, Musa S, Abu Kasim NH
    J Cell Mol Med, 2015 Mar;19(3):566-80.
    PMID: 25475098 DOI: 10.1111/jcmm.12381
    MicroRNAs (miRNAs) are small non-coding RNAs that regulate translation of mRNA into protein and play a crucial role for almost all biological activities. However, the identification of miRNAs from mesenchymal stem cells (MSCs), especially from dental pulp, is poorly understood. In this study, dental pulp stem cells (DPSCs) were characterized in terms of their proliferation and differentiation capacity. Furthermore, 104 known mature miRNAs were profiled by using real-time PCR. Notably, we observed 19 up-regulated miRNAs and 29 significantly down-regulated miRNAs in DPSCs in comparison with bone marrow MSCs (BM-MSCs). The 19 up-regulated miRNAs were subjected to ingenuity analysis, which were composed into 25 functional networks. We have chosen top 2 functional networks, which comprised 10 miRNA (hsa-miR-516a-3p, hsa-miR-125b-1-3p, hsa-miR-221-5p, hsa-miR-7, hsa-miR-584-5p, hsa-miR-190a, hsa-miR-106a-5p, hsa-mir-376a-5p, hsa-mir-377-5p and hsa-let-7f-2-3p). Prediction of target mRNAs and associated biological pathways regulated by each of this miRNA was carried out. We paid special attention to hsa-miR-516a-3p and hsa-miR-7-5p as these miRNAs were highly expressed upon validation with qRT-PCR analysis. We further proceeded with loss-of-function analysis with these miRNAs and we observed that hsa-miR-516a-3p knockdown induced a significant increase in the expression of WNT5A. Likewise, the knockdown of hsa-miR-7-5p increased the expression of EGFR. Nevertheless, further validation revealed the role of WNT5A as an indirect target of hsa-miR-516a-3p. These results provide new insights into the dynamic role of miRNA expression in DPSCs. In conclusion, using miRNA signatures in human as a prediction tool will enable us to elucidate the biological processes occurring in DPSCs.
  13. Abdullah M, Rahman FA, Gnanasegaran N, Govindasamy V, Abu Kasim NH, Musa S
    ScientificWorldJournal, 2014;2014:235941.
    PMID: 24616615 DOI: 10.1155/2014/235941
    Lead (Pb(2+)) exposure continues to be a significant public health problem. Therefore, it is vital to have a continuous epidemiological dataset for a better understanding of Pb(2+) toxicity. In the present study, we have exposed stem cells isolated from deciduous and permanent teeth, periodontal ligament, and bone marrow to five different types of Pb(2+) concentrations (160, 80, 40, 20, and 10 µM) for 24 hours to identify the adverse effects of Pb(2+) on the proliferation, differentiation, and gene expression on these cell lines. We found that Pb(2+) treatment altered the morphology and adhesion of the cells in a dose-dependent manner. There were no significant changes in terms of cell surface phenotypes. Cells exposed to Pb(2+) continued to differentiate into chondrogenesis and adipogenesis, and a severe downregulation was observed in osteogenesis. Gene expression studies revealed a constant expression of key markers associated with stemness (Oct 4, Rex 1) and DNA repair enzyme markers, but downregulation occurred with some ectoderm and endoderm markers, demonstrating an irregular and untimely differentiation trail. Our study revealed for the first time that Pb(2+) exposure not only affects the phenotypic characteristics but also induces significant alteration in the differentiation and gene expression in the cells.
  14. Musa S, Xin LZ, Govindasamy V, Fuen FW, Kasim NH
    Expert Opin Biol Ther, 2014 Jan;14(1):63-73.
    PMID: 24191782 DOI: 10.1517/14712598.2014.858694
    Acute myocardial infarction is the primary cause of heart disease-related death in the world. Reperfusion therapy is currently the backbone of treatment for acute myocardial infarction albeit with many limitations. With the emergence of stem cells as potential therapeutic agents, attempts in using them to enhance cardiac function have increased exponentially. However, it has its own disadvantages, and we postulate that the primary drawback is choosing the right cell type and solving this may significantly contribute to ambitious goal of using stem cells in the regeneration medicine.
  15. Srijaya TC, Pradeep PJ, Zain RB, Musa S, Abu Kasim NH, Govindasamy V
    Stem Cells Int, 2012;2012:423868.
    PMID: 22654919 DOI: 10.1155/2012/423868
    Induced pluripotent stem cell-based therapy for treating genetic disorders has become an interesting field of research in recent years. However, there is a paucity of information regarding the applicability of induced pluripotent stem cells in dental research. Recent advances in the use of induced pluripotent stem cells have the potential for developing disease-specific iPSC lines in vitro from patients. Indeed, this has provided a perfect cell source for disease modeling and a better understanding of genetic aberrations, pathogenicity, and drug screening. In this paper, we will summarize the recent progress of the disease-specific iPSC development for various human diseases and try to evaluate the possibility of application of iPS technology in dentistry, including its capacity for reprogramming some genetic orodental diseases. In addition to the easy availability and suitability of dental stem cells, the approach of generating patient-specific pluripotent stem cells will undoubtedly benefit patients suffering from orodental disorders.
  16. Alabsi AM, Ali R, Ali AM, Al-Dubai SA, Harun H, Abu Kasim NH, et al.
    Asian Pac J Cancer Prev, 2012;13(10):5131-6.
    PMID: 23244123
    Cancer is one of the major health problems worldwide and its current treatments have a number of undesired adverse side effects. Natural compounds may reduce these. Currently, a few plant products are being used to treat cancer. In this study, goniothalamin, a natural occurring styryl-lactone extracted from Goniothalamus macrophyllus, was investigated for cytotoxic properties against cervical cancer (HeLa), breast carcinoma (MCF-7) and colon cancer (HT29) cells as well as normal mouse fibroblast (3T3) using MTT assay. Fluorescence microscopy showed that GTN is able to induce apoptosis in HeLa cells in a time dependent manner. Flow cytometry further revealed HeLa cells treated with GTN to be arrested in the S phase. Phosphatidyl serine properties present during apoptosis enable early detection of the apoptosis in the cells. Using annexin V/PI double staining it could be shown that GTN induces early apoptosis on HeLa cells after 24, 48 and 72 h. It could be concluded that goniothalamin showing a promising cytotoxicity effect against several cancer cell lines including cervical cancer cells (HeLa) with apoptosis as the mode of cell death induced on HeLa cells by Goniothalamin was.
  17. Abu Kasim NH, Govindasamy V, Gnanasegaran N, Musa S, Pradeep PJ, Srijaya TC, et al.
    J Tissue Eng Regen Med, 2015 Dec;9(12):E252-66.
    PMID: 23229816 DOI: 10.1002/term.1663
    The discovery of mesenchymal stem cells (MSCs) from a myriad of tissues has triggered the initiative of establishing tailor-made stem cells for disease-specific therapy. Nevertheless, lack of understanding on the inherent differential propensities of these cells may restrict their clinical outcome. Therefore, a comprehensive study was done to compare the proliferation, differentiation, expression of cell surface markers and gene profiling of stem cells isolated from different sources, viz. bone marrow, Wharton's jelly, adipose tissue and dental pulp. We found that although all MSCs were phenotypically similar to each other, Wharton's jelly (WJ) MSCs and dental pulp stem cells (DPSCs) were highly proliferative as compared to bone marrow (BM) MSCs and adipose tissue (AD) MSCs. Moreover, indistinguishable cell surface characteristics and differentiation capacity were confirmed to be similar among all cell types. Based on gene expression profiling, we postulate that BM-MSCs constitutively expressed genes related to inflammation and immunodulation, whereas genes implicated in tissue development were highly expressed in AD-MSCs. Furthermore, the transcriptome profiling of WJ-MSCs and DPSCs revealed an inherent bias towards the neuro-ectoderm lineage. Based on our findings, we believe that there is no unique master mesenchymal stem cell that is appropriate to treat all target diseases. More precisely, MSCs from different sources exhibit distinct and unique gene expression signatures that make them competent to give rise to specific lineages rather than others. Therefore, stem cells should be subjected to rigorous characterization and utmost vigilance needs to be adopted in order to choose the best cellular source for a particular disease.
  18. Abd Rahman F, Mohd Ali J, Abdullah M, Abu Kasim NH, Musa S
    J. Periodontol., 2016 07;87(7):837-47.
    PMID: 26846966 DOI: 10.1902/jop.2016.150610
    BACKGROUND: This study investigates the effects of aspirin (ASA) on the proliferative capacity, osteogenic potential, and expression of growth factor-associated genes in periodontal ligament stem cells (PDLSCs).

    METHODS: Mesenchymal stem cells (MSCs) from PDL tissue were isolated from human premolars (n = 3). The MSCs' identity was confirmed by immunophenotyping and trilineage differentiation assays. Cell proliferation activity was assessed through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Polymerase chain reaction array was used to profile the expression of 84 growth factor-associated genes. Pathway analysis was used to identify the biologic functions and canonic pathways activated by ASA treatment. The osteogenic potential was evaluated through mineralization assay.

    RESULTS: ASA at 1,000 μM enhances osteogenic potential of PDLSCs. Using a fold change (FC) of 2.0 as a threshold value, the gene expression analyses indicated that 19 genes were differentially expressed, which includes 12 upregulated and seven downregulated genes. Fibroblast growth factor 9 (FGF9), vascular endothelial growth factor A (VEGFA), interleukin-2, bone morphogenetic protein-10, VEGFC, and 2 (FGF2) were markedly upregulated (FC range, 6 to 15), whereas pleotropin, FGF5, brain-derived neurotrophic factor, and Dickkopf WNT signaling pathway inhibitor 1 were markedly downregulated (FC 32). Of the 84 growth factor-associated genes screened, 35 showed high cycle threshold values (≥35).

    CONCLUSIONS: ASA modulates the expression of growth factor-associated genes and enhances osteogenic potential in PDLSCs. ASA upregulated the expression of genes that could activate biologic functions and canonic pathways related to cell proliferation, human embryonic stem cell pluripotency, tissue regeneration, and differentiation. These findings suggest that ASA enhances PDLSC function and may be useful in regenerative dentistry applications, particularly in the areas of periodontal health and regeneration.

  19. Goh SY, Khan SA, Tee KK, Abu Kasim NH, Yin WF, Chan KG
    Sci Rep, 2016;6:20702.
    PMID: 26860259 DOI: 10.1038/srep20702
    Cell-cell communication is also known as quorum sensing (QS) that happens in the bacterial cells with the aim to regulate their genes expression in response to increased cell density. In this study, a bacterium (L8A) isolated from dental plaque biofilm was identified as Citrobacter amalonaticus by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS). Its N-acylhomoserine-lactone (AHL) production was screened by using two types of AHL biosensors namely Chromobacterium violaceum CV026 and Escherichia coli [pSB401]. Citrobacter amalonaticus strain L8A was identified and confirmed producing numerous types of AHL namely N-butyryl-L-homoserine lactone (C4-HSL), N-hexanoyl-L-homoserine lactone (C6-HSL), N-octanoyl-L-homoserine lactone (C8-HSL) and N-hexadecanoyl-L-homoserine lactone (C16-HSL). We performed the whole genome sequence analysis of this oral isolate where its genome sequence reveals the presence of QS signal synthase gene and our work will pave the ways to study the function of the related QS genes in this bacterium.
  20. Jayaraman P, Govindasamy V, Gnanasegaran N, Kunasekaran W, Vasanthan P, Musa S, et al.
    Clin Oral Investig, 2016 Jan;20(1):109-16.
    PMID: 26048030 DOI: 10.1007/s00784-015-1497-1
    Long-term culture system is used to prevent the impediment of insufficient cells and is good for low starting materials such as dental pulp or periodontal ligament. In general, although cell viability and functionality are the most common aspects taken into consideration in culturing cells for a long term, they may not truly represent the biological state of the cells. Hence, we explored the behaviour of another important aspect which is the immune properties in long-term cultured cells.
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