Displaying publications 41 - 53 of 53 in total

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  1. Nanocomposites of iron oxide, sodium alginate, and eugenol induce apoptosis via PI3K/Akt/mTOR signaling in Hep3 cells and in vivo hepatotoxicity in the zebrafish model
    Elderdery AY, Alzerwi NAN, Alzahrani B, Alsrhani A, Alsultan A, Rayzah M, et al.
    Int J Biol Macromol, 2024 Jan;256(Pt 2):127490.
    PMID: 37979758 DOI: 10.1016/j.ijbiomac.2023.127490
    Hepatic cancer is among the most recurrently detected malignancies worldwide and one of the main contributors to cancer-associated mortality. With few available therapeutic choices, there is an instant necessity to explore suitable options. In this aspect, Nanotechnology has been employed to explore prospective chemotherapeutic approaches, especially for cancer treatment. Nanotechnology is concerned with the biological and physical properties of nanoparticles in the therapeutic use of drugs. In the current work, formulation, and characterization of α-Fe2O3-Sodium Alginate-Eugenol nanocomposites (FSE NCs) using several approaches like SEM and TEM, UV-visible, FTIR, and PL spectroscopy, XRD, EDAX, and DLS studies have been performed. With an average size of 50 nm, the rhombohedral structure of NCs was identified. Further, their anticancer activity against Hep3B liver cancer cell lines has been performed by cell viability, dual staining, DCFH-DA, Annexin-V/-FITC/PI, cell cycle analysis methods, and PI3K/Akt/mTOR signaling proteins were studied to assess the anticancer effects of the NCs in Hep3B cells. Also, anti-cancer activity on animal modeling in-vivo using zebra fishes to hematological parameters, liver enzymes, and histopathology study effectiveness was noticed. Moreover, the NCs reduced the viability, elevated the ROS accumulation, diminished the membrane integrity, reduced the antioxidants, blocked the cell cycle, and triggered the PI3K/Akt/mTOR signaling axis that eventually resulted in cell death. As a result, FSE NCs possess huge potential for use as a possible anticancer candidate.
  2. Metabolic utilization of human osteoblast cell line hFOB 1.19 under normoxic and hypoxic conditions: A phenotypic microarray analysis
    Cui YC, Qiu YS, Wu Q, Bu G, Peli A, Teh SW, et al.
    Exp Biol Med (Maywood), 2021 May;246(10):1177-1183.
    PMID: 33535809 DOI: 10.1177/1535370220985468
    Osteoblasts play an important role in bone regeneration and repair. The hypoxia condition in bone occurs when bone undergoes fracture, and this will trigger a series of biochemical and mechanical changes to enable bone repair. Hence, it is interesting to observe the metabolites and metabolism changes when osteoblasts are exposed to hypoxic condition. This study has looked into the response of human osteoblast hFOB 1.19 under normoxic and hypoxic conditions by observing the cell growth and utilization of metabolites via Phenotype MicroArrays™ under these two different oxygen concentrations. The cell growth of hFOB 1.19 under hypoxic condition showed better growth compared to hFOB 1.19 under normal condition. In this study, osteoblast used glycolysis as the main pathway to produce energy as hFOB 1.19 in both hypoxic and normoxic conditions showed cell growth in well containing dextrin, glycogen, maltotriose, D-maltose, D-glucose-6-phospate, D-glucose, D-mannose, D-Turanose, D-fructose-6-phosphate, D-galactose, uridine, adenosine, inosine and α-keto-glutaric acid. In hypoxia, the cells have utilized additional metabolites such as α-D-glucose-1-phosphate and D-fructose, indicating possible activation of glycogen synthesis and glycogenolysis to metabolize α-D-glucose-1-phosphate. Meanwhile, during normoxia, D-L-α-glycerol phosphate was used, and this implies that the osteoblast may use glycerol-3-phosphate shuttle and oxidative phosphorylation to metabolize glycerol-3-phosphate.
  3. Fulltext Micro-Computed Tomography Detection of Gold Nanoparticle-Labelled Mesenchymal Stem Cells in the Rat Subretinal Layer
    Mok PL, Leow SN, Koh AE, Mohd Nizam HH, Ding SL, Luu C, et al.
    Int J Mol Sci, 2017 Feb 08;18(2).
    PMID: 28208719 DOI: 10.3390/ijms18020345
    Mesenchymal stem cells are widely used in many pre-clinical and clinical settings. Despite advances in molecular technology; the migration and homing activities of these cells in in vivo systems are not well understood. Labelling mesenchymal stem cells with gold nanoparticles has no cytotoxic effect and may offer suitable indications for stem cell tracking. Here, we report a simple protocol to label mesenchymal stem cells using 80 nm gold nanoparticles. Once the cells and particles were incubated together for 24 h, the labelled products were injected into the rat subretinal layer. Micro-computed tomography was then conducted on the 15th and 30th day post-injection to track the movement of these cells, as visualized by an area of hyperdensity from the coronal section images of the rat head. In addition, we confirmed the cellular uptake of the gold nanoparticles by the mesenchymal stem cells using transmission electron microscopy. As opposed to other methods, the current protocol provides a simple, less labour-intensive and more efficient labelling mechanism for real-time cell tracking. Finally, we discuss the potential manipulations of gold nanoparticles in stem cells for cell replacement and cancer therapy in ocular disorders or diseases.
  4. Looking into dental pulp stem cells in the therapy of photoreceptors and retinal degenerative disorders
    Alsaeedi HA, Lam C, Koh AE, Teh SW, Mok PL, Higuchi A, et al.
    J. Photochem. Photobiol. B, Biol., 2020 Jan;203:111727.
    PMID: 31862637 DOI: 10.1016/j.jphotobiol.2019.111727
    Blindness and vision impairment are caused by irremediable retinal degeneration in affected individuals worldwide. Cell therapy for a retinal replacement can potentially rescue their vision, specifically for those who lost the light sensing photoreceptors in the eye. As such, well-characterized retinal cells are required for the replacement purposes. Stem cell-based therapy in photoreceptor and retinal pigment epithelium transplantation is well received, however, the drawbacks of retinal transplantation is the limited clinical protocols development, insufficient number of transplanted cells for recovery, the selection of potential stem cell sources that can be differentiated into the target cells, and the ability of cells to migrate to the host tissue. Dental pulp stem cells (DPSC) belong to a subset of mesenchymal stem cells, and are recently being studied due to its high capability of differentiating into cells of the neuronal lineage. In this review, we look into the potential uses of DPSC in treating retinal degeneration, and also the current data supporting its application.
  5. Retinal degeneration rat model: A study on the structural and functional changes in the retina following injection of sodium iodate
    Koh AE, Alsaeedi HA, Rashid MBA, Lam C, Harun MHN, Saleh MFBM, et al.
    J. Photochem. Photobiol. B, Biol., 2019 Jul;196:111514.
    PMID: 31154277 DOI: 10.1016/j.jphotobiol.2019.111514
    Retinal disorders account for a large proportion of ocular disorders that can lead to visual impairment or blindness, and yet our limited knowledge in the pathogenesis and choice of appropriate animal models for new treatment modalities may contribute to ineffective therapies. Although genetic in vivo models are favored, the variable expressivity and penetrance of these heterogeneous disorders can cause difficulties in assessing potential treatments against retinal degeneration. Hence, an attractive alternative is to develop a chemically-induced model that is both cost-friendly and standardizable. Sodium iodate is an oxidative chemical that is used to simulate late stage retinitis pigmentosa and age-related macular degeneration. In this study, retinal degeneration was induced through systemic administration of sodium iodate (NaIO3) at varying doses up to 80 mg/kg in Sprague-Dawley rats. An analysis on the visual response of the rats by electroretinography (ERG) showed a decrease in photoreceptor function with NaIO3 administration at a dose of 40 mg/kg or greater. The results correlated with the TUNEL assay, which revealed signs of DNA damage throughout the retina. Histomorphological analysis also revealed extensive structural lesions throughout the outer retina and parts of the inner retina. Our results provided a detailed view of NaIO3-induced retinal degeneration, and showed that the administration of 40 mg/kg NaIO3 was sufficient to generate disturbances in retinal function. The pathological findings in this model reveal a degenerating retina, and can be further utilized to develop effective therapies for RPE, photoreceptor, and bipolar cell regeneration.
  6. Fulltext Transplanted Erythropoietin-Expressing Mesenchymal Stem Cells Promote Pro-survival Gene Expression and Protect Photoreceptors From Sodium Iodate-Induced Cytotoxicity in a Retinal Degeneration Model
    Koh AE, Alsaeedi HA, Rashid MBA, Lam C, Harun MHN, Ng MH, et al.
    Front Cell Dev Biol, 2021;9:652017.
    PMID: 33987180 DOI: 10.3389/fcell.2021.652017
    Mesenchymal stem cells (MSC) are highly regarded as a potential treatment for retinal degenerative disorders like retinitis pigmentosa and age-related macular degeneration. However, donor cell heterogeneity and inconsistent protocols for transplantation have led to varied outcomes in clinical trials. We previously showed that genetically-modifying MSCs to express erythropoietin (MSCEPO) improved its regenerative capabilities in vitro. Hence, in this study, we sought to prove its potential in vivo by transplanting MSCsEPO in a rat retinal degeneration model and analyzing its retinal transcriptome using RNA-Seq. Firstly, MSCsEPO were cultured and expanded before being intravitreally transplanted into the sodium iodate-induced model. After the procedure, electroretinography (ERG) was performed bi-weekly for 30 days. Histological analyses were performed after the ERG assessment. The retina was then harvested for RNA extraction. After mRNA-enrichment and library preparation, paired-end RNA-Seq was performed. Salmon and DESeq2 were used to process the output files. The generated dataset was then analyzed using over-representation (ORA), functional enrichment (GSEA), and pathway topology analysis tools (SPIA) to identify enrichment of key pathways in the experimental groups. The results showed that the MSCEPO-treated group had detectable ERG waves (P <0.05), which were indicative of successful phototransduction. The stem cells were also successfully detected by immunohistochemistry 30 days after intravitreal transplantation. An initial over-representation analysis revealed a snapshot of immune-related pathways in all the groups but was mainly overexpressed in the MSC group. A subsequent GSEA and SPIA analysis later revealed enrichment in a large number of biological processes including phototransduction, regeneration, and cell death (P adj <0.05). Based on these pathways, a set of pro-survival gene expressions were extracted and tabulated. This study provided an in-depth transcriptomic analysis on the MSCEPO-treated retinal degeneration model as well as a profile of pro-survival genes that can be used as candidates for further genetic enhancement studies on stem cells.
  7. Fulltext Corrigendum: Transplanted Erythropoietin-Expressing Mesenchymal Stem Cells Promote Pro-survival Gene Expression and Protect Photoreceptors From Sodium Iodate-Induced Cytotoxicity in a Retinal Degeneration Model
    Koh AE, Alsaeedi HA, Rashid MBA, Lam C, Harun MHN, Ng MH, et al.
    Front Cell Dev Biol, 2021;9:764504.
    PMID: 34604245 DOI: 10.3389/fcell.2021.764504
    [This corrects the article DOI: 10.3389/fcell.2021.652017.].
  8. Fulltext Stem Cell Therapy in Dengue Virus-Infected BALB/C Mice Improves Hepatic Injury
    Sakinah S, Priya SP, Mok PL, Munisvaradass R, Teh SW, Sun Z, et al.
    Front Cell Dev Biol, 2021;9:637270.
    PMID: 34291043 DOI: 10.3389/fcell.2021.637270
    Extensive clinical efforts have been made to control the severity of dengue diseases; however, the dengue morbidity and mortality have not declined. Dengue virus (DENV) can infect and cause systemic damage in many organs, resulting in organ failure. Here, we present a novel report showing a tailored stem-cell-based therapy that can aid in viral clearance and rescue liver cells from further damage during dengue infection. We administered a combination of hematopoietic stem cells and endothelial progenitor cells in a DENV-infected BALB/c mouse model and found that delivery of this cell cocktail had improved their liver functions, confirmed by hematology, histopathology, and next-generation sequencing. These stem and progenitor cells can differentiate into target cells and repair the damaged tissues. In addition, the regime can regulate endothelial proliferation and permeability, modulate inflammatory reactions, enhance extracellular matrix production and angiogenesis, and secrete an array of growth factors to create an enhanced milieu for cell reparation. No previous study has been published on the treatment of dengue infection using stem cells combination. In conclusion, dengue-induced liver damage was rescued by administration of stem cell therapy, with less apoptosis and improved repair and regeneration in the dengue mouse model.
  9. Corrigendum: Stem Cell Therapy in Dengue Virus-Infected BALB/C Mice Improves Hepatic Injury
    Sakinah S, Priya SP, Mok PL, Munisvaradass R, Teh SW, Sun Z, et al.
    Front Cell Dev Biol, 2021;9:800659.
    PMID: 35178398 DOI: 10.3389/fcell.2021.800659
    [This corrects the article DOI: 10.3389/fcell.2021.637270.].
  10. Fulltext Synthesis, Characterization, and Antimicrobial and Antiproliferative Effects of CuO-TiO2-Chitosan-Escin Nanocomposites on Human Leukemic MOLT4 Cells
    Elderdery AY, Alhamidi AH, Elkhalifa AME, Althobiti MM, Eltayeb Omer N, Alsugoor MH, et al.
    Nanomaterials (Basel), 2022 Oct 26;12(21).
    PMID: 36364538 DOI: 10.3390/nano12213753
    Nanocomposites comprised of CuO-TiO2-chitosan-escin, which has adjustable physicochemical properties, provide a solution for therapeutic selectivity in cancer treatment. By controlling the intrinsic signaling primarily through the mitochondrial signaling pathway, we desired nanocomposites with enhanced anticancer activity by containing CuO-TiO2-chitosan-escin. The metal oxides CuO and TiO2, the natural polymer chitosan, and a phytochemical compound escin were combined to form CuO-TiO2-chitosan-escin nanocomposites. The synthesized nanocomposites were confirmed and characterized using FTIR spectroscopy, TEM, and UV-Vis absorption spectroscopy. A human leukemia cell line (MOLT-4) was used to assess the efficacy and selectivity of nanocomposites. Based on a cytotoxicity study, CuO-TiO2-chitosan-escin nanocomposites had inhibition concentrations (IC50) of 13.68, 8.9, and 7.14 µg/mL against human T lymphoblast cells after 24, 48, and 72 h of incubation, respectively. Compared with untreated MOLT-4 cells, CuO-TiO2-chitosan-escin nanocomposite-treated cells significantly increased (p < 0.05) caspase-3, -8, and -9 and decreased the levels of antioxidant enzymes GR, SOD, and GSH. Furthermore, MDA for lipid peroxidase and ROS levels significantly increased (p < 0.05) in the treated cells than in the untreated cells. Remarkably, CuO-TiO2-chitosan-escin nanocomposite-mediated control of cell cycles were mainly achieved through the activation of caspase-3, -8, and -9.
  11. Fulltext Modulatory and regenerative potential of transplanted bone marrow-derived mesenchymal stem cells on rifampicin-induced kidney toxicity
    Danjuma L, Mok PL, Higuchi A, Hamat RA, Teh SW, Koh AE, et al.
    Regen Ther, 2018 Dec;9:100-110.
    PMID: 30525080 DOI: 10.1016/j.reth.2018.09.001
    INTRODUCTION: Anti-tuberculosis agent rifampicin is extensively used for its effectiveness. Possible complications of tuberculosis and prolonged rifampicin treatment include kidney damage; these conditions can lead to reduced efficiency of the affected kidney and consequently to other diseases. Bone marrow-derived mesenchymal stem cells (BMMSCs) can be used in conjunction with rifampicin to avert kidney damage; because of its regenerative and differentiating potentials into kidney cells. This research was designed to assess the modulatory and regenerative potentials of MSCs in averting kidney damage due to rifampicin-induced kidney toxicity in Wistar rats and their progenies. BMMSCs used in this research were characterized according to the guidelines of International Society for Cellular Therapy.

    METHODS: The rats (male and female) were divided into three experimental groups, as follows: Group 1: control rats (4 males & 4 females); Group 2: rats treated with rifampicin only (4 males & 4 females); and Group 3: rats treated with rifampicin plus MSCs (4 males & 4 females). Therapeutic doses of rifampicin (9 mg/kg/day for 3-months) and MSCs infusions (twice/month for 3-months) were administered orally and intravenously respectively. At the end of the three months, the animals were bred together to determine if the effects would carry over to the next generation. Following breeding, the rats were sacrificed to harvest serum for biochemical analysis and the kidneys were also harvested for histological analysis and quantification of the glomeruli size, for the adult rats and their progenies.

    RESULTS: The results showed some level of alterations in the biochemical indicators and histopathological damage in the rats that received rifampicin treatment alone, while the control and stem cells treated group showed apparently normal to nearly normal levels of both bio-indicators and normal histological architecture.

    CONCLUSIONS: Intravenous administration of MSCs yielded sensible development, as seen from biochemical indicators, histology and the quantitative cell analysis, hence implying the modulatory and regenerative properties of MSCs.

  12. Fulltext Hematological Findings among COVID-19 Patients Attending King Khalid Hospital at Najran, Kingdom of Saudi Arabia
    Elkhalifa AME, Elderdery AY, Al Bataj IA, Tamomh AG, Alyami MM, Almakrami HA, et al.
    Biomed Res Int, 2022;2022:4620037.
    PMID: 35224093 DOI: 10.1155/2022/4620037
    COVID-19 is a global pandemic viral infection that has affected millions worldwide. Limited data is available on the effect of COVID-19 on hematological parameters in Saudi Arabia. This study is aimed at examining the role of hematological parameters among COVID-19 patients admitted to King Khalid Hospital in Najran, Saudi Arabia. This is a retrospective, hospital-based study of 514 cases who were recruited during August to October 2020. 257 COVID-19 patients formed the study group, and a further 257 negative subjects formed the control group. Anemia was significantly elevated in positive subjects over controls (respectively, 64.2% and 35.8%), with patients 2.5 times more likely to be anemic (p < 0.01). Thrombocytopenia was higher in patients over controls (respectively, 62% and 38%), with patients ~1.7 times more likely to be thrombocytopenic (p < 0.01). Moreover, leukopenia was significantly higher in patients over controls (respectively, 71% and 29%), with positive subjects ~2.6 times more likely to be leukopenic. Our study results indicate that mild anemia associated with leukopenia may have diagnostic value for COVID-19. Careful assessment of hematological parameters, at baseline and throughout the disease path, will assist physicians in formulating personalized approaches to treatment and promptly offer intensive care to those in greater need.
  13. Dental pulp stem cells therapy overcome photoreceptor cell death and protects the retina in a rat model of sodium iodate-induced retinal degeneration
    Alsaeedi HA, Koh AE, Lam C, Rashid MBA, Harun MHN, Saleh MFBM, et al.
    J. Photochem. Photobiol. B, Biol., 2019 Sep;198:111561.
    PMID: 31352000 DOI: 10.1016/j.jphotobiol.2019.111561
    Blindness and vision loss contribute to irreversible retinal degeneration, and cellular therapy for retinal cell replacement has the potential to treat individuals who have lost light sensitive photoreceptors in the retina. Retinal cells are well characterized in function, and are a subject of interest in cellular replacement therapy of photoreceptors and the retinal pigment epithelium. However, retinal cell transplantation is limited by various factors, including the choice of potential stem cell source that can show variability in plasticity as well as host tissue integration. Dental pulp is one such source that contains an abundance of stem cells. In this study we used dental pulp-derived mesenchymal stem cells (DPSCs) to mitigate sodium iodate (NaIO3) insult in a rat model of retinal degeneration. Sprague-Dawley rats were first given an intravitreal injection of 3 × 105 DPSCs as well as a single systemic administration of NaIO3 (40 mg/kg). Electroretinography (ERG) was performed for the next two months and was followed-up by histological analysis. The ERG recordings showed protection of DPSC-treated retinas within 4 weeks, which was statistically significant (* P ≤ .05) compared to the control. Retinal thickness of the control was also found to be thinner (*** P ≤ .001). The DPSCs were found integrated in the photoreceptor layer through immunohistochemical staining. Our findings showed that DPSCs have the potential to moderate retinal degeneration. In conclusion, DPSCs are a potential source of stem cells in the field of eye stem cell therapy due to its protective effects against retinal degeneration.
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