Displaying publications 41 - 53 of 53 in total

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  1. Leow SN, Luu CD, Hairul Nizam MH, Mok PL, Ruhaslizan R, Wong HS, et al.
    PLoS One, 2015;10(6):e0128973.
    PMID: 26107378 DOI: 10.1371/journal.pone.0128973
    To investigate the safety and efficacy of subretinal injection of human Wharton's Jelly-derived mesenchymal stem cells (hWJ-MSCs) on retinal structure and function in Royal College of Surgeons (RCS) rats.
  2. Alam MK, Alfawzan AA, Haque S, Mok PL, Marya A, Venugopal A, et al.
    Front Pediatr, 2021;9:651951.
    PMID: 34026687 DOI: 10.3389/fped.2021.651951
    To investigate whether the craniofacial sagittal jaw relationship in patients with non-syndromic cleft differed from non-cleft (NC) individuals by artificial intelligence (A.I.)-driven lateral cephalometric (Late. Ceph.) analysis. The study group comprised 123 subjects with different types of clefts including 29 = BCLP (bilateral cleft lip and palate), 41 = UCLP (unilateral cleft lip and palate), 9 = UCLA (unilateral cleft lip and alveolus), 13 = UCL (unilateral cleft lip) and NC = 31. The mean age was 14.77 years. SNA, SNB, ANB angle and Wits appraisal was measured in lateral cephalogram using a new innovative A.I driven Webceph software. Two-way ANOVA and multiple-comparison statistics tests were applied to see the differences between gender and among different types of clefts vs. NC individuals. A significant decrease (p < 0.005) in SNA, ANB, Wits appraisal was observed in different types of clefts vs. NC individuals. SNB (p > 0.005) showed insignificant variables in relation to type of clefts. No significant difference was also found in terms of gender in relation to any type of clefts and NC group. The present study advocates a decrease in sagittal development (SNA, ANB and Wits appraisal) in different types of cleft compared to NC individuals.
  3. Alzahrani B, Elderdery AY, Alsrhani A, Alzerwi NAN, Althobiti MM, Elkhalifa AME, et al.
    Int J Biol Macromol, 2023 Jul 31;244:125054.
    PMID: 37245766 DOI: 10.1016/j.ijbiomac.2023.125054
    The present study investigated the cytotoxicity and proapoptotic properties of iron oxide-sodium-alginate-thymoquinone nanocomposites against breast cancer MDA-MB-231 cells in vitro and in silico. This study used chemical synthesis to formulate the nanocomposite. Electron microscopies such as scanning (SEM) and transmission (TEM), Fourier transform infrared (FT-IR), Ultraviolet-Visible, Photoluminescence spectroscopy, selected area (electron) diffraction (SAED), energy dispersive X-ray analysis (EDX), and X-ray diffraction studies (XRD) were used to characterize the synthesized ISAT-NCs and the average size of them was found to be 55 nm. To evaluate the cytotoxic, antiproliferative, and apoptotic potentials of ISAT-NCs on MDA-MB-231 cells, MTT assays, FACS-based cell cycle studies, annexin-V-PI staining, ELISA, and qRT-PCR were used. PI3K-Akt-mTOR receptors and thymoquinone were predicted using in-silico docking studies. Cell proliferation is reduced in MDA-MB-231 cells due to ISAT-NC cytotoxicity. As a result of FACS analysis, ISAT-NCs had nuclear damage, ROS production, and elevated annexin-V levels, which resulted in cell cycle arrest in the S phase. The ISAT-NCs in MDA-MB-231 cells were found to downregulate PI3K-Akt-mTOR regulatory pathways in the presence of inhibitors of PI3K-Akt-mTOR, showing that these regulatory pathways are involved in apoptotic cell death. We also predicted the molecular interaction between thymoquinone and PI3K-Akt-mTOR receptor proteins using in-silico docking studies which also support PI3K-Akt-mTOR signaling inhibition by ISAT-NCs in MDA-MB-231 cells. As a result of this study, we can conclude that ISAT-NCs inhibit the PI3K-Akt-mTOR pathway in breast cancer cell lines, causing apoptotic cell death.
  4. Sivan PP, Syed S, Mok PL, Higuchi A, Murugan K, Alarfaj AA, et al.
    Stem Cells Int, 2016;2016:8304879.
    PMID: 27293447 DOI: 10.1155/2016/8304879
    Sustenance of visual function is the ultimate focus of ophthalmologists. Failure of complete recovery of visual function and complications that follow conventional treatments have shifted search to a new form of therapy using stem cells. Stem cell progenitors play a major role in replenishing degenerated cells despite being present in low quantity and quiescence in our body. Unlike other tissues and cells, regeneration of new optic cells responsible for visual function is rarely observed. Understanding the transcription factors and genes responsible for optic cells development will assist scientists in formulating a strategy to activate and direct stem cells renewal and differentiation. We review the processes of human eye development and address the strategies that have been exploited in an effort to regain visual function in the preclinical and clinical state. The update of clinical findings of patients receiving stem cell treatment is also presented.
  5. 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.
  6. Ali F, Taresh S, Al-Nuzaily M, Mok PL, Ismail A, Ahmad S
    Eur Rev Med Pharmacol Sci, 2016 Oct;20(20):4390-4400.
    PMID: 27831631
    Numerous lines of evidence support that bone marrow is a rich source of stem cells that can be used for research purposes and to treat some complex blood diseases and cancers. Stem cells are a potential source for regenerative medicine and tissue replacement after injury or disease, and mother cells that possess the capacity to become any type of cell in the body. They are cells without specific structure and characterized by their ability to self-renew or multiply while maintaining the potential to develop into other types of cells. Stem cells can normally become cells of the blood, heart, bones, skin, muscles or brain. Although, there are different sources of stem cells, all types of stem cells have the same capacity to develop into multiple types of cells. Stem cells are generally described as unspecialized cells with unlimited proliferation capacity that can divide (through mitosis) to produce more stem cells. Several types of adult stem cells have been characterized and can be cultured in vitro, including neural stem cells, hematopoietic stem cells, mesenchymal stem cells, cardiac stem cells and epithelial stem cells. They are valuable as research tools and might, in the future, be used to treat a wide range of diseases such as hematological hereditary diseases, Parkinson's disease, diabetes mellitus, heart disease and many other diseases. Currently, two types of stem cells have been identified based on their origins, namely embryonic stem cells and adult stem cells. Collectively, although many kinds of literature have been studying stem cell application in terms of clinical practice, stem cell-based therapy is still in its infancy stage.
  7. Al-Sanea MM, Ali Khan MS, Abdelazem AZ, Lee SH, Mok PL, Gamal M, et al.
    Molecules, 2018 Jan 31;23(2).
    PMID: 29385071 DOI: 10.3390/molecules23020297
    A new series of 1-phenyl-3-(4-(pyridin-3-yl)phenyl)urea derivatives were synthesized and subjected to in vitro antiproliferative screening against National Cancer Institute (NCI)-60 human cancer cell lines of nine different cancer types. Fourteen compounds 5a-n were synthesized with three different solvent exposure moieties (4-hydroxylmethylpiperidinyl and trimethoxyphenyloxy and 4-hydroxyethylpiperazine) attached to the core structure. Substituents with different π and σ values were added on the terminal phenyl group. Compounds 5a-e with a 4-hydroxymethylpiperidine moiety showed broad-spectrum antiproliferative activity with higher mean percentage inhibition values over the 60-cell line panel at 10 µM concentration. Compound 5a elicited lethal rather than inhibition effects on SK-MEL-5 melanoma cell line, 786-0, A498, RXF 393 renal cancer cell lines, and MDA-MB-468 breast cancer cell line. Two compounds, 5a and 5d showed promising mean growth inhibitions and thus were further tested at five-dose mode to determine median inhibitory concentration (IC50) values. The data revealed that urea compounds 5a and 5d are the most active derivatives, with significant efficacies and superior potencies than paclitaxel in 21 different cancer cell lines belonging particularly to renal cancer and melanoma cell lines. Moreover, 5a and 5d had superior potencies than gefitinib in 38 and 34 cancer cell lines, respectively, particularly colon cancer, breast cancer and melanoma cell lines.
  8. Elderdery AY, Alzahrani B, Hamza SMA, Mostafa-Hedeab G, Mok PL, Subbiah SK
    Bioinorg Chem Appl, 2022;2022:5949086.
    PMID: 36212987 DOI: 10.1155/2022/5949086
    Leukemia is the most prevalent cancer in children and one of the most common and deadly cancers that affect adults. Several metal oxide nanoparticles, biopolymers, and phytochemicals have been discovered to target cancer cells selectively while inflicting low to no damage to healthy cells. Among the existing nanoparticle synthesis methodologies, biologically synthesized nanoparticles using phytochemicals have emerged as a straightforward, economical, and environmentally sound strategy. The synergistic antitumor potential of ZnO-TiO2-chitosan-farnesol nanocomposites (NCs) against leukemia MOLT-4 cells was investigated in the current study. After synthesizing the NCs, characterization of the same was carried out using XRD, DLS, FESEM, TEM, PL, EDX, and FTIR spectroscopy. To analyze its anticancer activity, MOLT-4 cells were cultured and treated at diverse dosages of NCs. The cell viability upon treatment was examined by MTT assay. The morphological and nuclear modifications were observed by dual staining. ROS and MMP levels were observed by DCFH-DA staining and Rh-123 dye, respectively. Furthermore, the caspase 3, 8, and 9 levels were examined by performing ELISA. The XRD patterns exhibited a hexagonal structure of the NCs. In the DLS spectrum, the hydrodynamic diameter of the NCs was observed to be 126.2 nm. The electrostatic interface between the ZnO-TiO2-chitosan-farnesol NCs was confirmed by the FTIR spectra. A significant loss of cell viability in a dosage-dependent trend confirmed the cytotoxic effect of the NCs. An elevated ROS level and MMP depletion suggested apoptosis-associated cell death via the intrinsic pathway, which was confirmed by elevated expressions of caspase 3, 8, and 9 markers. Thus, the results showed that the synthesized NCs demonstrated a remarkable anticancer potential against leukemic cells and can be potentially valuable in cancer treatments. The findings from this study conclude that this is a new approach for modifying the physicochemical characteristics of ZnO-TiO2-chitosan-farnesol composites to increase their properties and synergistically exhibit anticancer properties in human leukemic cancer cells.
  9. 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.
  10. Rayzah M, Elderdery AY, Alzerwi NAN, Alzahrani B, Alsrhani A, Alsultan A, et al.
    Plants (Basel), 2023 Sep 05;12(18).
    PMID: 37765338 DOI: 10.3390/plants12183174
    An aqueous extract of Syzygium cumini seeds was utilized to green synthesize titanium dioxide nanoparticles (TiO2 NPs). UV-Visible, DLS, FTIR, XRD, FESEM, TEM, SAED, EDAX, and photoluminescence spectroscopy techniques were employed to characterize the prepared TiO2 nanoparticles. The rutile crystal structure of TiO2 NPs was revealed by XRD study. The TEM and FESEM images of the TiO2 NPs revealed an average particle size of 50-100 nm. We employed EDAX to investigate the elemental compositions of TiO2 NPs. The O-Ti-O stretching bands appeared in the FTIR spectrum of TiO2 NPs at wavenumbers of 495 cm-1. The absorption edge peaks of TiO2 NPs were found in the UV-vis spectra at 397 nm. The MTT study revealed that TiO2 NPs effectively inhibited the growth of liver cancer Hep3 and Hep-G2 cells. The results of the corresponding fluorescent staining assays showed that TiO2 NPs significantly increased ROS generation, decreased MMP, and induced apoptosis in both liver cancer Hep3 and Hep-G2 cells. TiO2 nanoparticles lessened SOD, CAT, and GSH levels while augmenting MDA contents in Hep3 and Hep-G2 cells. In both Hep3 and Hep-G2 cells treated with TiO2 NPs, the Bax, CytC, p53, caspase-3, -8, and -9 expressions were remarkably augmented, while Bcl-2 expression was reduced. Overall, these findings revealed that formulated TiO2 NPs treatment considerably inhibited growth and triggered apoptosis in Hep3 and HepG2 cells.
  11. Alsrhani A, Elderdery AY, Alzahrani B, Alzerwi NAN, Althobiti MM, Rayzah M, et al.
    Molecules, 2023 Apr 04;28(7).
    PMID: 37049991 DOI: 10.3390/molecules28073228
    Breast cancer is among the most recurrent malignancies, and its prevalence is rising. With only a few treatment options available, there is an immediate need to search for better alternatives. In this regard, nanotechnology has been applied to develop potential chemotherapeutic techniques, particularly for cancer therapy. Specifically, albumin-based nanoparticles are a developing platform for the administration of diverse chemotherapy drugs owing to their biocompatibility and non-toxicity. Visnagin, a naturally derived furanochromone, treats cancers, epilepsy, angina, coughs, and inflammatory illnesses. In the current study, the synthesis and characterization of albumin visnagin (AV) nanoparticles (NPs) using a variety of techniques such as transmission electron microscopy, UV-visible, Fourier transform infrared, energy dispersive X-ray composition analysis, field emission scanning electron microscopy, photoluminescence, X-Ray diffraction, and dynamic light scattering analyses have been carried out. The MTT test, dual AO/EB, DCFH-DA, Annexin-V-FITC/PI, Propidium iodide staining techniques as well as analysis of apoptotic proteins, antioxidant enzymes, and PI3K/Akt/mTOR signaling analysis was performed to examine the NPs' efficacy to suppress MDA-MB-468 cell lines. The NPs decreased cell viability increased the amount of ROS in the cells, disrupted membrane integrity, decreased the level of antioxidant enzymes, induced cell cycle arrest, and activated the PI3K/Akt/mTOR signaling cascade, ultimately leading to cell death. Thus, AV NPs possesses huge potential to be employed as a strong anticancer therapy alternative.
  12. 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.
  13. Farhana A, Koh AE, Kothandan S, Alsrhani A, Mok PL, Subbiah SK
    Int J Mol Sci, 2021 Nov 13;22(22).
    PMID: 34830168 DOI: 10.3390/ijms222212286
    Cancer cells are able to proliferate in an unregulated manner. There are several mechanisms involved that propel such neoplastic transformations. One of these processes involves bypassing cell death through changes in gene expression and, consequently, cell growth. This involves a complex epigenetic interaction within the cell, which drives it towards oncogenic transformations. These epigenetic events augment cellular growth by potentially altering chromatin structures and influencing key gene expressions. Therapeutic mechanisms have been developed to combat this by taking advantage of the underlying oncogenic mechanisms through chemical modulation. Camptothecin (CPT) is an example of this type of drug. It is a selective topoisomerase I inhibitor that is effective against many cancers, such as colorectal cancer. Previously, we successfully formulated a magnetic nanocarrier-conjugated CPT with β-cyclodextrin and iron NPs (Fe3O4) cross-linked using EDTA (CPT-CEF). Compared to CPT alone, it boasts higher efficacy due to its selective targeting and increased solubility. In this study, we treated HT29 colon cancer cells with CPT-CEF and attempted to investigate the cytotoxic effects of the formulation through an epigenetic perspective. By using RNA-Seq, several differentially expressed genes were obtained (p < 0.05). Enrichr was then used for the over-representation analysis, and the genes were compared to the epigenetic roadmap and histone modification database. The results showed that the DEGs had a high correlation with epigenetic modifications involving histone H3 acetylation. Furthermore, a subset of these genes was shown to be associated with the Wnt/β-catenin signaling pathway, which is highly upregulated in a large number of cancer cells. These genes could be investigated as downstream therapeutic targets against the uncontrolled proliferation of cancer cells. Further interaction analysis of the identified genes with the key genes of the Wnt/β-catenin signaling pathway in colorectal cancer identified the direct interactors and a few transcription regulators. Further analysis in cBioPortal confirmed their genetic alterations and their distribution across patient samples. Thus, the findings of this study reveal that colorectal cancer could be reversed by treatment with the CPT-CEF nanoparticle-conjugated nanocarrier through an epigenetic mechanism.
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