Displaying publications 1 - 20 of 105 in total

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  1. Fulltext Zyxin regulates embryonic stem cell fate by modulating mechanical and biochemical signaling interface
    Zhang S, Chong LH, Woon JYX, Chua TX, Cheruba E, Yip AK, et al.
    Commun Biol, 2023 Jan 18;6(1):62.
    PMID: 36653484 DOI: 10.1038/s42003-023-04421-0
    Biochemical signaling and mechano-transduction are both critical in regulating stem cell fate. How crosstalk between mechanical and biochemical cues influences embryonic development, however, is not extensively investigated. Using a comparative study of focal adhesion constituents between mouse embryonic stem cell (mESC) and their differentiated counterparts, we find while zyxin is lowly expressed in mESCs, its levels increase dramatically during early differentiation. Interestingly, overexpression of zyxin in mESCs suppresses Oct4 and Nanog. Using an integrative biochemical and biophysical approach, we demonstrate involvement of zyxin in regulating pluripotency through actin stress fibres and focal adhesions which are known to modulate cellular traction stress and facilitate substrate rigidity-sensing. YAP signaling is identified as an important biochemical effector of zyxin-induced mechanotransduction. These results provide insights into the role of zyxin in the integration of mechanical and biochemical cues for the regulation of embryonic stem cell fate.
    Matched MeSH terms: Embryonic Stem Cells/metabolism
  2. Fulltext Human non-small cell lung cancer expresses putative cancer stem cell markers and exhibits the transcriptomic profile of multipotent cells
    Zakaria N, Yusoff NM, Zakaria Z, Lim MN, Baharuddin PJ, Fakiruddin KS, et al.
    BMC Cancer, 2015;15:84.
    PMID: 25881239 DOI: 10.1186/s12885-015-1086-3
    Despite significant advances in staging and therapies, lung cancer remains a major cause of cancer-related lethality due to its high incidence and recurrence. Clearly, a novel approach is required to develop new therapies to treat this devastating disease. Recent evidence indicates that tumours contain a small population of cells known as cancer stem cells (CSCs) that are responsible for tumour maintenance, spreading and resistant to chemotherapy. The genetic composition of CSCs so far is not fully understood, but manipulation of the specific genes that maintain their integrity would be beneficial for developing strategies to combat cancer. Therefore, the goal of this study isto identify the transcriptomic composition and biological functions of CSCs from non-small cell lung cancer (NSCLC).
    Matched MeSH terms: Neoplastic Stem Cells/metabolism*
  3. Amniotic Membrane Enhance the Effect of Vascular Endothelial Growth Factor on the Angiogenic Marker Expression of Stem Cells from Human Exfoliated Deciduous Teeth
    Yusof MFH, Hashim SNM, Zahari W, Chandra H, Noordin KBAA, Kannan TP, et al.
    Appl Biochem Biotechnol, 2020 May;191(1):177-190.
    PMID: 32096060 DOI: 10.1007/s12010-020-03266-1
    Previously, it was reported that human amniotic membrane (AM) induced stem cells from human deciduous exfoliated teeth (SHED) endothelial-like-cell differentiation. This interesting effect of AM matrix on SHED demands further elucidation. Objective of this in vitro work was to study the effect of 24-h VEGF induced on SHED endothelial differentiation when seeded on acellular stromal side (SS) of AM matrix. Stemness of SHED was identified by flow cytometry. Cell attachment and morphological changes towards the matrix was observed by scanning electron microscopy. Protein expression of endothelial marker was examined by Western blot. The expression of stem cells and endothelial-specific gene markers of VEGF-induced SHED cultured on human AM was inspected via reverse transcriptase-polymerase chain reaction. Results showed SHED at both passages retain stemness property. Ang-1 protein was expressed in SHED. Cells treated with VEGF and cultured on AM transformed attached well to AM. VEGF-induced SHED expressed both stem cell and endothelial-specific markers throughout the treatments and timeline. Interestingly, prolonged VEGF treatment increased the expression of Cox-2 and VE-Cadherin genes in all treated groups when compared to SHED. It was concluded that the VEGF-induced SHED showed better expression of endothelial-specific markers when cultured on SS of AM, with prolonged VEGF treatment.
    Matched MeSH terms: Stem Cells/metabolism*
  4. Fulltext Phenotypic and functional characterization of long-term cryopreserved human adipose-derived stem cells
    Yong KW, Pingguan-Murphy B, Xu F, Abas WA, Choi JR, Omar SZ, et al.
    Sci Rep, 2015;5:9596.
    PMID: 25872464 DOI: 10.1038/srep09596
    Cryopreservation represents an effective technique to maintain the functional properties of human adipose-derived stem cells (ASCs) and allows pooling of cells via long-term storage for clinical applications, e.g., cell-based therapies. It is crucial to reduce freezing injury during the cryopreservation process by loading the ASCs with the optimum concentration of suitable cryoprotective agents (CPAs). In this study, human ASCs were preserved for 3 months in different combinations of CPAs, including 1) 0.25 M trehalose; 2) 5% dimethylsulfoxide (DMSO); 3) 10% DMSO; 4) 5% DMSO + 20% fetal bovine serum (FBS); 5) 10% DMSO + 20% FBS; 6) 10% DMSO + 90% FBS. Interestingly, even with a reduction of DMSO to 5% and without FBS, cryopreserved ASCs maintained high cell viability comparable with standard cryomedium (10% DMSO + 90% FBS), with normal cell phenotype and proliferation rate. Cryopreserved ASCs also maintained their differentiation capability (e.g., to adipocytes, osteocytes and chondrocytes) and showed an enhanced expression level of stemness markers (e.g., NANOG, OCT-4, SOX-2 and REX-1). Our findings suggest that 5% DMSO without FBS may be an ideal CPA for an efficient long-term cryopreservation of human ASCs. These results aid in establishing standardized xeno-free long-term cryopreservation of human ASCs for clinical applications.
    Matched MeSH terms: Adult Stem Cells/metabolism*
  5. Fulltext Pluripotent Human embryonic stem cell derived neural lineages for in vitro modelling of enterovirus 71 infection and therapy
    Yap MS, Tang YQ, Yeo Y, Lim WL, Lim LW, Tan KO, et al.
    Virol J, 2016 Jan 06;13:5.
    PMID: 26738773 DOI: 10.1186/s12985-015-0454-6
    The incidence of neurological complications and fatalities associated with Hand, Foot & Mouth disease has increased over recent years, due to emergence of newly-evolved strains of Enterovirus 71 (EV71). In the search for new antiviral therapeutics against EV71, accurate and sensitive in vitro cellular models for preliminary studies of EV71 pathogenesis is an essential prerequisite, before progressing to expensive and time-consuming live animal studies and clinical trials.
    Matched MeSH terms: Neural Stem Cells/metabolism
  6. Sonic Hedgehog Regulation of the Neural Precursor Cell Fate During Chicken Optic Tectum Development
    Yang C, Li X, Li Q, Li H, Qiao L, Guo Z, et al.
    J Mol Neurosci, 2018 Feb;64(2):287-299.
    PMID: 29285739 DOI: 10.1007/s12031-017-1019-5
    During nervous system development, neurons project axons over long distances to reach the appropriate targets for correct neural circuit formation. Sonic hedgehog (Shh) is a secreted protein and plays a key role in regulating vertebrate embryogenesis, especially in central nervous system (CNS) patterning, including neuronal migration and axonal projection in the brain and spinal cord. In the developing ventral midbrain, Shh is sufficient to specify a striped pattern of cell fates. Little is known about the molecular mechanisms underlying the Shh regulation of the neural precursor cell fate during the optic tectum development. Here, we aimed at studying how Shh might regulate chicken optic tectum patterning. In the present study, in ovo electroporation methods were employed to achieve the overexpression of Shh in the optic tectum during chicken embryo development. Besides, the study combined in ovo electroporation and neuron isolation culturing to study the function of Shh in vivo and in vitro. The fluorescent immunohistochemistry methods were used to check the related indicators. The results showed that Shh overexpression caused 87.8% of cells to be distributed to the stratum griseum central (SGC) layer, while only 39.3% of the GFP-transfected cells resided in the SGC layer in the control group. Shh overexpression also reduced the axon length in vivo and in vitro. In conclusion, we provide evidence that Shh regulates the neural precursor cell fate during chicken optic tectum development. Shh overexpression impairs neuronal migration and may affect the fate determination of transfected neurons.
    Matched MeSH terms: Neural Stem Cells/metabolism*
  7. Therapeutic potentials of neural stem cells in Alzheimer's disease
    Wong RSY, Cheong SK
    Malays J Pathol, 2020 Aug;42(2):157-170.
    PMID: 32860368
    The commonest cause of dementia among the elderly population is Alzheimer's disease (AD). It is a health concern globally as the number of people affected by dementia worldwide is rapidly increasing. Several genes have been linked to AD and the pathogenesis of the disease has been extensively and vigorously examined. Thus far, only a few drugs have been approved by the Food and Drug Administration (FDA) for the pharmacological treatment of AD and a growing body of research has turned to alternative options such as stem cell therapy. This review will give an overview of the pathological and clinical aspects of AD. Although researchers have explored the suitability and feasibility of using various types of stems cells to treat AD, this review will focus mainly on neural stem cells (NSCs)/ neural progenitor cells (NPCs). The behaviour and properties of NSCs will be described, accompanied by a comprehensive discussion of the therapeutic strategies involving the use of NSCs/NPCs in the treatment of the disease.
    Matched MeSH terms: Stem Cells/metabolism
  8. Fulltext Extrinsic factors involved in the differentiation of stem cells into insulin-producing cells: an overview
    Wong RS
    Exp Diabetes Res, 2011;2011:406182.
    PMID: 21747828 DOI: 10.1155/2011/406182
    Diabetes mellitus is a chronic disease with many debilitating complications. Treatment of diabetes mellitus mainly revolves around conventional oral hypoglycaemic agents and insulin replacement therapy. Recently, scientists have turned their attention to the generation of insulin-producing cells (IPCs) from stem cells of various sources. To date, many types of stem cells of human and animal origins have been successfully turned into IPCs in vitro and have been shown to exert glucose-lowering effect in vivo. However, scientists are still faced with the challenge of producing a sufficient number of IPCs that can in turn produce sufficient insulin for clinical use. A careful choice of stem cells, methods, and extrinsic factors for induction may all be contributing factors to successful production of functional beta-islet like IPCs. It is also important that the mechanism of differentiation and mechanism by which IPCs correct hyperglycaemia are carefully studied before they are used in human subjects.
    Matched MeSH terms: Stem Cells/metabolism
  9. The Promises and Pitfalls of CRISPR-Mediated Base Editing in Stem Cells
    Wong PK, Mohamad Zamberi NN, Syafruddin SE, Cheah FC, Azmi N, Law JX, et al.
    CRISPR J, 2023 Jun;6(3):196-215.
    PMID: 37219623 DOI: 10.1089/crispr.2023.0013
    Stem cells such as induced pluripotent stem cells, embryonic stem cells, and hematopoietic stem and progenitor cells are growing in importance in disease modeling and regenerative medicine. The applications of CRISPR-based gene editing to create a mélange of disease and nondisease stem cell lines have further enhanced the utility of this innately versatile group of cells in the studies of human genetic disorders. Precise base edits can be achieved using a variety of CRISPR-centric approaches, particularly homology-directed repair and the recently developed base editors and prime editors. Despite its much-touted potential, editing single DNA bases is technically challenging. In this review, we discuss the strategies for achieving exact base edits in the creation of various stem cell-based models for use in elucidating disease mechanisms and assessing drug efficacy, and the unique characteristics of stem cells that warrant special considerations.
    Matched MeSH terms: Embryonic Stem Cells/metabolism
  10. Interplay of autophagy and cancer stem cells in hepatocellular carcinoma
    Wong MM, Chan HY, Aziz NA, Ramasamy TS, Bong JJ, Ch'ng ES, et al.
    Mol Biol Rep, 2021 Apr;48(4):3695-3717.
    PMID: 33893928 DOI: 10.1007/s11033-021-06334-9
    Liver cancer is the sixth most common cancer and the fourth leading cause of cancer deaths in the world. The most common type of liver cancers is hepatocellular carcinoma (HCC). Autophagy is the cellular digestion of harmful components by sequestering the waste products into autophagosomes followed by lysosomal degradation for the maintenance of cellular homeostasis. The impairment of autophagy is highly associated with the development and progression of HCC although autophagy may be involved in tumour-suppressing cellular events. In regards to its protecting role, autophagy also shelters the cells from anoikis- a programmed cell death in anchorage-dependent cells detached from the surrounding extracellular matrix which facilitates metastasis in HCC. Liver cancer stem cells (LCSCs) have the ability for self-renewal and differentiation and are associated with the development and progression of HCC by regulating stemness, resistance and angiogenesis. Interestingly, autophagy is also known to regulate normal stem cells by promoting cellular survival and differentiation and maintaining cellular homeostasis. In this review, we discuss the basal autophagic mechanisms and double-faceted roles of autophagy as both tumour suppressor and tumour promoter in HCC, as well as its association with and contribution to self-renewal and differentiation of LCSCs.
    Matched MeSH terms: Neoplastic Stem Cells/metabolism*
  11. Fulltext Tryptophan-metabolizing gut microbes regulate adult neurogenesis via the aryl hydrocarbon receptor
    Wei GZ, Martin KA, Xing PY, Agrawal R, Whiley L, Wood TK, et al.
    Proc Natl Acad Sci U S A, 2021 Jul 06;118(27).
    PMID: 34210797 DOI: 10.1073/pnas.2021091118
    While modulatory effects of gut microbes on neurological phenotypes have been reported, the mechanisms remain largely unknown. Here, we demonstrate that indole, a tryptophan metabolite produced by tryptophanase-expressing gut microbes, elicits neurogenic effects in the adult mouse hippocampus. Neurogenesis is reduced in germ-free (GF) mice and in GF mice monocolonized with a single-gene tnaA knockout (KO) mutant Escherichia coli unable to produce indole. External administration of systemic indole increases adult neurogenesis in the dentate gyrus in these mouse models and in specific pathogen-free (SPF) control mice. Indole-treated mice display elevated synaptic markers postsynaptic density protein 95 and synaptophysin, suggesting synaptic maturation effects in vivo. By contrast, neurogenesis is not induced by indole in aryl hydrocarbon receptor KO (AhR-/-) mice or in ex vivo neurospheres derived from them. Neural progenitor cells exposed to indole exit the cell cycle, terminally differentiate, and mature into neurons that display longer and more branched neurites. These effects are not observed with kynurenine, another AhR ligand. The indole-AhR-mediated signaling pathway elevated the expression of β-catenin, Neurog2, and VEGF-α genes, thus identifying a molecular pathway connecting gut microbiota composition and their metabolic function to neurogenesis in the adult hippocampus. Our data have implications for the understanding of mechanisms of brain aging and for potential next-generation therapeutic opportunities.
    Matched MeSH terms: Neural Stem Cells/metabolism
  12. The changes of stemness biomarkers expression in human adipose-derived stem cells during long-term manipulation
    Wan Safwani WK, Makpol S, Sathapan S, Chua KH
    Biotechnol Appl Biochem, 2011 Jul-Aug;58(4):261-70.
    PMID: 21838801 DOI: 10.1002/bab.38
    One of the advantages of human adipose-derived stem cells (ASCs) in regenerative medicine is that they can be harvested in abundance. However, the stemness biomarkers, which marked the safety and efficacy of ASCs in accordance with the good manufacturing practice guidelines, is not yet well established. This study was designed to investigate the effect of long-term culture on the stemness properties of ASCs using quantitative real-time polymerase chain reaction and flow cytometry. Results showed the growth rate of ASCs was at its peak when they reached P10 (population doubling; PD = 26) but started to decrease when they were expanded to P15 (PD = 36) and P20 (PD = 46). The ASCs can be culture expanded with minimal alteration in the stemness genes and cluster of differentiation (CD) markers expression up to P10. Expression level of Sox2, Nestin, and Nanog3 was significantly decreased at later passage. CD31, CD45, CD117, and human leukocyte antigen DR, DQ, and DP were lowly expressed at P5 and P10 but their expressions increased significantly at P15 or P20. The differentiation ability of ASCs (adipogenesis, osteogenesis, and neurogenesis) also decreased in long-term culture. Our findings suggested that P10 (PD = 26) should be the "cutoff point" for clinical usage because ASCs at passage 15 onward showed significant changes in the stemness genes, CD markers expression, and differentiation capability.
    Matched MeSH terms: Stem Cells/metabolism*
  13. Fulltext 5-Azacytidine is insufficient for cardiogenesis in human adipose-derived stem cells
    Wan Safwani WK, Makpol S, Sathapan S, Chua KH
    J Negat Results Biomed, 2012;11:3.
    PMID: 22221649 DOI: 10.1186/1477-5751-11-3
    Adipose tissue is a source of multipotent adult stem cells and it has the ability to differentiate into several types of cell lineages such as neuron cells, osteogenic cells and adipogenic cells. Several reports have shown adipose-derived stem cells (ASCs) have the ability to undergo cardiomyogenesis. Studies have shown 5-azacytidine can successfully drive stem cells such as bone marrow derived stem cells to differentiate into cardiomyogenic cells. Therefore, in this study, we investigated the effect 5-azacytidine on the cardiogenic ability of ASCs.
    Matched MeSH terms: Stem Cells/metabolism; Embryonic Stem Cells/metabolism
  14. Fulltext Annatto-derived tocotrienol stimulates osteogenic activity in preosteoblastic MC3T3-E1 cells: a temporal sequential study
    Wan Hasan WN, Abd Ghafar N, Chin KY, Ima-Nirwana S
    Drug Des Devel Ther, 2018;12:1715-1726.
    PMID: 29942115 DOI: 10.2147/DDDT.S168935
    PURPOSE: Annatto-derived tocotrienol (AnTT) has been shown to improve bone formation in animal models of osteoporosis. However, detailed studies of the effects of AnTT on preosteoblastic cells were limited. This study was conducted to investigate the osteogenic effect of AnTT on preosteoblast MC3T3-E1 cells in a time-dependent manner.

    MATERIALS AND METHODS: Murine MC3T3-E1 preosteoblastic cells were cultured in the different concentrations of AnTT (0.001-1 µg/mL) up to 24 days. Expression of osteoblastic differentiation markers was measured by qPCR (osterix [OSX], collagen 1 alpha 1 [COL1α1], alkaline phosphatase [ALP], and osteocalcin [OCN]) and by fluorometric assay for ALP activity. Detection of collagen and mineralized nodules was done via Direct Red staining and Alizarin Red staining, respectively.

    RESULTS: The results showed that osteoblastic differentiation-related genes, such as OSX, COL1α1, ALP, and OCN, were significantly increased in the AnTT-treated groups compared to the vehicle group in a time-dependent manner (P<0.05). Type 1 collagen level was increased from day 3 to day 15 in the AnTT-treated groups, while ALP activity was increased from day 9 to day 21 in the AnTT-treated groups (P<0.05). Enhanced mineralization was observed in the AnTT-treated groups via increasing Alizarin Red staining from day 3 to day 21 (P<0.05).

    CONCLUSION: Our results suggest that AnTT enhances the osteogenic activity by promoting the bone formation-related genes and proteins in a temporal and sequential manner.

    Matched MeSH terms: Stem Cells/metabolism
  15. The evaluation expression of non-coding RNAs in response to HSV-G47∆ oncolytic virus infection in glioblastoma multiforme cancer stem cells
    Vazifehmand R, Ali DS, Othman Z, Chau DM, Stanslas J, Shafa M, et al.
    J Neurovirol, 2022 Dec;28(4-6):566-582.
    PMID: 35951174 DOI: 10.1007/s13365-022-01089-w
    Glioblastoma multiforme is the most aggressive astrocytes brain tumor. Glioblastoma cancer stem cells and hypoxia conditions are well-known major obstacles in treatment. Studies have revealed that non-coding RNAs serve a critical role in glioblastoma progression, invasion, and resistance to chemo-radiotherapy. The present study examined the expression levels of microRNAs (in normoxic condition) and long non-coding RNAs (in normoxic and hypoxic conditions) in glioblastoma stem cells treated with the HSV-G47∆. The expression levels of 43 miRNAs and 8 lncRNAs isolated from U251-GBM-CSCs were analyzed using a miRCURY LNA custom PCR array and a quantitative PCR assay, respectively. The data revealed that out of 43 miRNAs that only were checked in normoxic condition, the only 8 miRNAs, including miR-7-1, miR-let-7b, miR-130a, miR-137, miR-200b, miR-221, miR-222, and miR-874, were markedly upregulated. The expression levels of lncRNAs, including LEF1 antisense RNA 1 (LEF1-AS1), metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), long intergenic non-protein coding RNA 470 (LINC00470), tumor suppressor candidate 7 (TUSC7), HOX transcript antisense RNA (HOTAIR), nuclear paraspeckle assembly transcript 1 (NEAT1), and X inactive specific transcript (XIST), were markedly downregulated in the hypoxic microenvironment, and H19-imprinted maternally expressed transcript (H19) was not observed to be dysregulated in this environment. Under normoxic conditions, LEF1-AS1, MALAT1, LINC00470, H19, HOTAIR, NEAT1, and XIST were downregulated and TUSC7 was not targeted by HSV-G47∆. Overall, the present data shows HSVG47Δ treatment deregulates non-coding RNA expression in GBM-CSC tumor microenvironments.
    Matched MeSH terms: Neoplastic Stem Cells/metabolism
  16. The evaluation of cartilage differentiations using transforming growth factor beta3 alone and with combination of bone morphogenetic protein-6 on adult stem cells
    Ude CC, Chen HC, Norhamdan MY, Azizi BM, Aminuddin BS, Ruszymah BHI
    Cell Tissue Bank, 2017 Sep;18(3):355-367.
    PMID: 28667462 DOI: 10.1007/s10561-017-9638-1
    In our quest to standardize our formula for a clinical trial, transforming growth factor-beta3 (TGF-β3) alone and in combination with bone morphogenetic protein-6 (BMP-6) were evaluated for their effectiveness in cartilage differentiation. Bone Marrow Stem Cells (BMSCs) and Adipose Derived Stem Cells (ADSCs) were induced to chondrogenic lineage using two different media. Native chondrocytes served as positive control. ADSCs and BMSCs proved multipotency by tri-lineage differentiations. ADSC has significantly higher growth kinetics compare to Chondrocyte only p ≤ 0.05. Using TGF-β3 alone, BMSC revealed higher expressions for hyaline cartilage genes compare to ADSCs. Chondrocyte has significantly higher early chondrogenic markers expression to ADSCs and BMSCs, while BMSCs was only higher to ADSC at chondroadherin, p ≤ 0.0001. On mature chondrogenic markers, chondrocytes were significantly higher to ADSCs and BMSCs for aggrecan, collagen IX, sry (sex determining region y)-box9, collagen II and fibromodullin; and only to ADSC for collagen XI. BMSC was higher to ADSC for aggrecan and collagen IX, p ≤ 0.0001. The combination of TGF-β3 + BMP-6 revealed increased gene expressions on both BMSCs and ADSCs for early and mature chondrogenic markers, but no significance difference. For dedifferentiation markers, ADSC was significantly higher to chondrocyte for collagen I. Glycosaminoglycan evaluations with both formulas revealed that chondrocytes were significantly higher to ADSCs and BMSCs, but none was significant to each other, p ≤ 0.0001. Combination of 10 ng TGF-β3 with 10 ng of BMP-6 enhanced chondrogenic potentials of BMSCs and ADSCs compare to TGF-β3 alone. This could be the ideal cocktail for either cell's chondrogenic induction.
    Matched MeSH terms: Adult Stem Cells/metabolism
  17. Fulltext Differential protein expression between chondrogenic differentiated MSCs, undifferentiated MSCs and adult chondrocytes derived from Oryctolagus cuniculus in vitro
    Tay LX, Lim CK, Mansor A, Kamarul T
    Int J Med Sci, 2014;11(1):24-33.
    PMID: 24396283 DOI: 10.7150/ijms.7244
    This preliminary study aims to determine the differentially expressed proteins from chondrogenic differentiated multipotent stromal cells (cMSCs) in comparison to undifferentiated multipotent stromal cells (MSCs) and adult chondrocytes (ACs).
    Matched MeSH terms: Multipotent Stem Cells/metabolism*
  18. An insight into the associations between microRNA expression and mitochondrial functions in cancer cell and cancer stem cell
    Tan WL, Subha ST, Mohtarrudin N, Cheah YK
    Mol Biol Rep, 2023 Jun;50(6):5395-5405.
    PMID: 37074612 DOI: 10.1007/s11033-023-08421-5
    The self-renew ability of cancer stem cells (CSCs) continues to challenge our determination for accomplishing cancer therapy breakthrough. Ineffectiveness of current cancer therapies to eradicate CSCs has contributed to chemoresistance and tumor recurrence. Yet, the discoveries of highly effective therapies have not been thoroughly developed. Further insights into cancer metabolomics and gene-regulated mechanisms of mitochondria in CSCs can expedite the development of novel anticancer drugs. In cancer cells, the metabolism is reprogrammed from oxidative phosphorylation (OXPHOS) to glycolysis. This alteration allows the cancer cell to receive continuous energy supplies and avoid apoptosis. The pyruvate obtained from glycolysis produces acetyl-coenzyme A (Acetyl-CoA) via oxidative decarboxylation and enters the tricarboxylic acid cycle for adenosine triphosphate generation. Mitochondrial calcium ion (Ca2+) uptake is responsible for mitochondrial physiology regulation, and reduced uptake of Ca2+  inhibits apoptosis and enhances cell survival in cancer. There have been many discoveries of mitochondria-associated microRNAs (miRNAs) stimulating the metabolic alterations in mitochondria via gene regulation which promote cancer cell survival. These miRNAs are also found in CSCs where they regulate genes and activate different mechanisms to destroy the mitochondria and enhance CSCs survival. By targeting the miRNAs that induced mitochondrial destruction, the mitochondrial functions can be restored; thus, it triggers CSCs apoptosis and completely eliminates the CSCs. In general, this review article aims to address the associations between miRNAs with mitochondrial activities in cancer cells and cancer stem cells that support cancer cell survival and self-renewal.
    Matched MeSH terms: Neoplastic Stem Cells/metabolism
  19. Fulltext Tualang honey improves human corneal epithelial progenitor cell migration and cellular resistance to oxidative stress in vitro
    Tan JJ, Azmi SM, Yong YK, Cheah HL, Lim V, Sandai D, et al.
    PLoS One, 2014;9(5):e96800.
    PMID: 24802273 DOI: 10.1371/journal.pone.0096800
    Stem cells with enhanced resistance to oxidative stress after in vitro expansion have been shown to have improved engraftment and regenerative capacities. Such cells can be generated by preconditioning them with exposure to an antioxidant. In this study we evaluated the effects of Tualang honey (TH), an antioxidant-containing honey, on human corneal epithelial progenitor (HCEP) cells in culture. Cytotoxicity, gene expression, migration, and cellular resistance to oxidative stress were evaluated. Immunofluorescence staining revealed that HCEP cells were holoclonal and expressed epithelial stem cell marker p63 without corneal cytokeratin 3. Cell viability remained unchanged after cells were cultured with 0.004, 0.04, and 0.4% TH in the medium, but it was significantly reduced when the concentration was increased to 3.33%. Cell migration, tested using scratch migration assay, was significantly enhanced when cells were cultured with TH at 0.04% and 0.4%. We also found that TH has hydrogen peroxide (H2O2) scavenging ability, although a trace level of H2O2 was detected in the honey in its native form. Preconditioning HCEP cells with 0.4% TH for 48 h showed better survival following H2O2-induced oxidative stress at 50 µM than untreated group, with a significantly lower number of dead cells (15.3 ± 0.4%) were observed compared to the untreated population (20.5 ± 0.9%, p<0.01). Both TH and ascorbic acid improved HCEP viability following induction of 100 µM H2O2, but the benefit was greater with TH treatment than with ascorbic acid. However, no significant advantage was demonstrated using 5-hydroxymethyl-2-furancarboxaldehyde, a compound that was found abundant in TH using GC/MS analysis. This suggests that the cellular anti-oxidative capacity in HCEP cells was augmented by native TH and was attributed to its antioxidant properties. In conclusion, TH possesses antioxidant properties and can improve cell migration and cellular resistance to oxidative stress in HCEP cells in vitro.
    Matched MeSH terms: Stem Cells/metabolism
  20. Fulltext 5' isomiR variation is of functional and evolutionary importance
    Tan GC, Chan E, Molnar A, Sarkar R, Alexieva D, Isa IM, et al.
    Nucleic Acids Res, 2014 Aug;42(14):9424-35.
    PMID: 25056318 DOI: 10.1093/nar/gku656
    We have sequenced miRNA libraries from human embryonic, neural and foetal mesenchymal stem cells. We report that the majority of miRNA genes encode mature isomers that vary in size by one or more bases at the 3' and/or 5' end of the miRNA. Northern blotting for individual miRNAs showed that the proportions of isomiRs expressed by a single miRNA gene often differ between cell and tissue types. IsomiRs were readily co-immunoprecipitated with Argonaute proteins in vivo and were active in luciferase assays, indicating that they are functional. Bioinformatics analysis predicts substantial differences in targeting between miRNAs with minor 5' differences and in support of this we report that a 5' isomiR-9-1 gained the ability to inhibit the expression of DNMT3B and NCAM2 but lost the ability to inhibit CDH1 in vitro. This result was confirmed by the use of isomiR-specific sponges. Our analysis of the miRGator database indicates that a small percentage of human miRNA genes express isomiRs as the dominant transcript in certain cell types and analysis of miRBase shows that 5' isomiRs have replaced canonical miRNAs many times during evolution. This strongly indicates that isomiRs are of functional importance and have contributed to the evolution of miRNA genes.
    Matched MeSH terms: Stem Cells/metabolism
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