Displaying publications 441 - 460 of 3311 in total

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  1. Fulltext Comparative Flavivirus-Host Protein Interaction Mapping Reveals Mechanisms of Dengue and Zika Virus Pathogenesis
    Shah PS, Link N, Jang GM, Sharp PP, Zhu T, Swaney DL, et al.
    Cell, 2018 Dec 13;175(7):1931-1945.e18.
    PMID: 30550790 DOI: 10.1016/j.cell.2018.11.028
    Mosquito-borne flaviviruses, including dengue virus (DENV) and Zika virus (ZIKV), are a growing public health concern. Systems-level analysis of how flaviviruses hijack cellular processes through virus-host protein-protein interactions (PPIs) provides information about their replication and pathogenic mechanisms. We used affinity purification-mass spectrometry (AP-MS) to compare flavivirus-host interactions for two viruses (DENV and ZIKV) in two hosts (human and mosquito). Conserved virus-host PPIs revealed that the flavivirus NS5 protein suppresses interferon stimulated genes by inhibiting recruitment of the transcription complex PAF1C and that chemical modulation of SEC61 inhibits DENV and ZIKV replication in human and mosquito cells. Finally, we identified a ZIKV-specific interaction between NS4A and ANKLE2, a gene linked to hereditary microcephaly, and showed that ZIKV NS4A causes microcephaly in Drosophila in an ANKLE2-dependent manner. Thus, comparative flavivirus-host PPI mapping provides biological insights and, when coupled with in vivo models, can be used to unravel pathogenic mechanisms.
    Matched MeSH terms: HEK293 Cells
  2. Fulltext Keyhole limpet hemocyanin augmented the killing activity, cytokine production and proliferation of NK cells, and inhibited the proliferation of Meth A sarcoma cells in vitro
    Sarker MM, Zhong M
    Indian J Pharmacol, 2014 Jan-Feb;46(1):40-5.
    PMID: 24550583 DOI: 10.4103/0253-7613.125164
    Keyhole limpet hemocyanin (KLH) is a popular tumor vaccine carrier protein and an immunostimulant. The present study aimed to investigate the immunoregulatory activity of KLH on cytotoxicity, cytokines production, and proliferation of natural killer (NK) cells. Moreover, antiproliferative activity of KLH on Meth A sarcoma cells was studied.
    Matched MeSH terms: Killer Cells, Natural/cytology; Killer Cells, Natural/drug effects*; Killer Cells, Natural/metabolism
  3. Fulltext Monoamine Oxidase Inhibition by Major Tanshinones from Salvia miltiorrhiza and Selective Muscarinic Acetylcholine M4 Receptor Antagonism by Tanshinone I
    Prajapati R, Park SE, Seong SH, Paudel P, Fauzi FM, Jung HA, et al.
    Biomolecules, 2021 Jul 08;11(7).
    PMID: 34356625 DOI: 10.3390/biom11071001
    Monoamine oxidases (MAOs) and muscarinic acetylcholine receptors (mAChRs) are considered important therapeutic targets for Parkinson's disease (PD). Lipophilic tanshinones are major phytoconstituents in the dried roots of Salvia miltiorrhiza that have demonstrated neuroprotective effects against dopaminergic neurotoxins and the inhibition of MAO-A. Since MAO-B inhibition is considered an effective therapeutic strategy for PD, we tested the inhibitory activities of three abundant tanshinone congeners against recombinant human MAO (hMAO) isoenzymes through in vitro experiments. In our study, tanshinone I (1) exhibited the highest potency against hMAO-A, followed by tanshinone IIA and cryptotanshinone, with an IC50 less than 10 µM. They also suppressed hMAO-B activity, with an IC50 below 25 µM. Although tanshinones are known to inhibit hMAO-A, their enzyme inhibition mechanism and binding sites have yet to be investigated. Enzyme kinetics and molecular docking studies have revealed the mode of inhibition and interactions of tanshinones during enzyme inhibition. Proteochemometric modeling predicted mAChRs as possible pharmacological targets of 1, and in vitro functional assays confirmed the selective M4 antagonist nature of 1 (56.1% ± 2.40% inhibition of control agonist response at 100 µM). These findings indicate that 1 is a potential therapeutic molecule for managing the motor dysfunction and depression associated with PD.
    Matched MeSH terms: CHO Cells
  4. Fulltext Amenable epigenetic traits of dental pulp stem cells underlie high capability of xeno-free episomal reprogramming
    Thekkeparambil Chandrabose S, Sriram S, Subramanian S, Cheng S, Ong WK, Rozen S, et al.
    Stem Cell Res Ther, 2018 03 20;9(1):68.
    PMID: 29559008 DOI: 10.1186/s13287-018-0796-2
    BACKGROUND: While a shift towards non-viral and animal component-free methods of generating induced pluripotent stem (iPS) cells is preferred for safer clinical applications, there is still a shortage of reliable cell sources and protocols for efficient reprogramming.

    METHODS: Here, we show a robust episomal and xeno-free reprogramming strategy for human iPS generation from dental pulp stem cells (DPSCs) which renders good efficiency (0.19%) over a short time frame (13-18 days).

    RESULTS: The robustness of DPSCs as starting cells for iPS induction is found due to their exceptional inherent stemness properties, developmental origin from neural crest cells, specification for tissue commitment, and differentiation capability. To investigate the epigenetic basis for the high reprogramming efficiency of DPSCs, we performed genome-wide DNA methylation analysis and found that the epigenetic signature of DPSCs associated with pluripotent, developmental, and ecto-mesenchymal genes is relatively close to that of iPS and embryonic stem (ES) cells. Among these genes, it is found that overexpression of PAX9 and knockdown of HERV-FRD improved the efficiencies of iPS generation.

    CONCLUSION: In conclusion, our study provides underlying epigenetic mechanisms that establish a robust platform for efficient generation of iPS cells from DPSCs, facilitating industrial and clinical use of iPS technology for therapeutic needs.

    Matched MeSH terms: Cells, Cultured; Mesenchymal Stromal Cells/cytology*; Mesenchymal Stromal Cells/metabolism
  5. Parameterisation and cellular evaluation of poly(ethylene) oxide-coated erbium oxide in MCF-7 cells as MRI diagnostic nanofibres
    Jamil M, Mustafa IS, Sahul Hamid SB, Ahmed NM, Khazaalah TH, Godwin E, et al.
    Colloids Surf B Biointerfaces, 2023 Aug;228:113423.
    PMID: 37390675 DOI: 10.1016/j.colsurfb.2023.113423
    The novelty of this work is the conjugation of poly(ethylene) oxide (PEO) with the erbium oxide (Er2O3) nanoparticles using the electrospinning technique. In this work, synthesised PEO-coated Er2O3 nanofibres were characterised and evaluated for their cytotoxicity to assess their potential use as diagnostic nanofibres for magnetic resonance imaging (MRI). PEO has significantly impacted nanoparticle conductivity due to its lower ionic conductivity at room temperature. The findings showed that the surface roughness was improved over the nanofiller loading, implying an improvement in cell attachment. The release profile performed for drug-controlling purposes has demonstrated a stable release after 30 min. Cellular response in MCF-7 cells showed high biocompatibility of the synthesised nanofibres. The cytotoxicity assay results showed that the diagnostic nanofibres had excellent biocompatibility, indicating the feasibility for diagnosis purposes. With excellent contrast performance, the PEO-coated Er2O3 nanofibres developed novel T2 and T1-T2 dual-mode MRI diagnostic nanofibres leading to better cancer diagnosis. In conclusion, this work has demonstrated that the conjugation of PEO-coated Er2O3 nanofibres improved the surface modification of the Er2O3 nanoparticles as a potential diagnostic agent. Using PEO in this study as a carrier or polymer matrix significantly influenced the biocompatibility and internalisation efficiency of the Er2O3 nanoparticles without triggering any morphological changes after treatment. This work has suggested permissible concentrations of PEO-coated Er2O3 nanofibres for diagnostic uses.
    Matched MeSH terms: MCF-7 Cells
  6. Sunni Islamic perspectives on lab-grown sperm and eggs derived from stem cells - in vitro gametogenesis (IVG)
    Serour G, Ghaly M, Saifuddeen SM, Anwar A, Isa NM, Chin AHB
    New Bioeth, 2023 Jun;29(2):108-120.
    PMID: 36427532 DOI: 10.1080/20502877.2022.2142094
    An exciting development in the field of assisted reproductive technologies is In Vitro Gametogenesis (IVG) that enables production of functional gametes from stem cells in the laboratory. Currently, development of this technology is still at an early stage and has demonstrated to work only in rodents. Upon critically examining the ethical dimensions of various possible IVG applications in human fertility treatment from a Sunni Islamic perspective, together with benefit-harm (maslahah-mafsadah) assessment; it is concluded that utilization of IVG, once its efficacy and safety are guaranteed, could be permissible by strictly adhering to Islamic ethical principles related to marriage, biological/genetic relatedness, sexual intercourse, and moral status of the embryo/fetus versus that of the gamete. As a result, IVG will be acceptable for treating primary infertility, age-related infertility, and preventing genetic diseases. However, it will be unacceptable for application in posthumous reproduction, donor gametes, genetic enhancement, and procreation in same-sex couples.
    Matched MeSH terms: Stem Cells
  7. Fulltext MicroRNA 299-3p modulates replicative senescence in endothelial cells
    Jong HL, Mustafa MR, Vanhoutte PM, AbuBakar S, Wong PF
    Physiol Genomics, 2013 Apr 1;45(7):256-67.
    PMID: 23362143 DOI: 10.1152/physiolgenomics.00071.2012
    MicroRNAs (miRNAs) regulate various cellular processes. While several genes associated with replicative senescence have been described in endothelial cells, miRNAs that regulate these genes remain largely unknown. The present study was designed to identify miRNAs associated with replicative senescence and their target genes in human umbilical vein endothelial cells (HUVECs). An integrated miRNA and gene profiling approach revealed that hsa-miR-299-3p is upregulated in senescent HUVECs compared with the young cells, and one of its target genes could be IGF1. IGF1 was upregulated in senescent compared with young HUVECs, and knockdown of hsa-miR-299-3p dose-dependently increased the mRNA expression of IGF1, more significantly observed in the presenescent cells (passage 19) compared with the senescent cells (passage 25). Knockdown of hsa-miR-299-3p also resulted in significant reduction in the percentage of cells positively stained for senescence-associated β-galactosidase and increases in cell viability measured by MTT assay but marginal increases in cell proliferation and cell migration capacity measured by real-time growth kinetics analysis. Moreover, knockdown of hsa-miR-299-3p also increased proliferation of cells treated with H2O2 to induce senescence. These findings suggest that hsa-miR-299-3p may delay or protect against replicative senescence by improving the metabolic activity of the senesced cells but does not stimulate growth of the remaining cells in senescent cultures. Hence, these findings provide an early insight into the role of hsa-miR-299-3p in the modulation of replicative senescence in HUVECs.
    Matched MeSH terms: Cells, Cultured; Human Umbilical Vein Endothelial Cells/metabolism; Human Umbilical Vein Endothelial Cells/physiology*
  8. Fulltext Scalable Production of Extracellular Vesicles and Its Therapeutic Values: A Review
    Ng CY, Kee LT, Al-Masawa ME, Lee QH, Subramaniam T, Kok D, et al.
    Int J Mol Sci, 2022 Jul 20;23(14).
    PMID: 35887332 DOI: 10.3390/ijms23147986
    Extracellular vesicles (EVs) are minute vesicles with lipid bilayer membranes. EVs are secreted by cells for intercellular communication. Recently, EVs have received much attention, as they are rich in biological components such as nucleic acids, lipids, and proteins that play essential roles in tissue regeneration and disease modification. In addition, EVs can be developed as vaccines against cancer and infectious diseases, as the vesicle membrane has an abundance of antigenic determinants and virulent factors. EVs for therapeutic applications are typically collected from conditioned media of cultured cells. However, the number of EVs secreted by the cells is limited. Thus, it is critical to devise new strategies for the large-scale production of EVs. Here, we discussed the strategies utilized by researchers for the scalable production of EVs. Techniques such as bioreactors, mechanical stimulation, electrical stimulation, thermal stimulation, magnetic field stimulation, topographic clue, hypoxia, serum deprivation, pH modification, exposure to small molecules, exposure to nanoparticles, increasing the intracellular calcium concentration, and genetic modification have been used to improve the secretion of EVs by cultured cells. In addition, nitrogen cavitation, porous membrane extrusion, and sonication have been utilized to prepare EV-mimetic nanovesicles that share many characteristics with naturally secreted EVs. Apart from inducing EV production, these upscaling interventions have also been reported to modify the EVs' cargo and thus their functionality and therapeutic potential. In summary, it is imperative to identify a reliable upscaling technique that can produce large quantities of EVs consistently. Ideally, the produced EVs should also possess cargo with improved therapeutic potential.
    Matched MeSH terms: Cells, Cultured
  9. Isolation of Primary Porcine Bronchial Epithelial Cells for Nipah Virus Infections
    Elvert M, Sauerhering L, Heiner A, Maisner A
    Methods Mol Biol, 2023;2682:103-120.
    PMID: 37610577 DOI: 10.1007/978-1-0716-3283-3_8
    The Malaysian strain of Nipah virus (NiV) first emerged in 1998/99 and caused a major disease outbreak in pigs and humans. While humans developed fatal encephalitis due to a prominent infection of brain microvessels, NiV-infected pigs mostly suffered from an acute respiratory disease and efficiently spread the infection via airway secretions. To elucidate the molecular basis of the highly productive NiV replication in porcine airways in vitro, physiologically relevant cell models that have maintained functional characteristics of airway epithelia in vivo are needed. Here, we describe in detail the method of isolating bronchial epithelial cells (PBEpC) from pig lungs that can be used for NiV infection studies. After the dissection of primary bronchia and removal of the mucus and protease digestion, bronchi segments are cut open and epithelial cells are scraped off and seeded on collagen-coated cell culture flasks. With this method, it is possible to isolate about 2 × 106 primary cells from the primary bronchi of one pig lung which can be cryopreserved or further subcultured. PBEpC form polarized monolayers on Transwell membrane inserts as controlled by immunostainings of epithelial marker proteins. NiV infection causes rapid formation of syncytia, allowing productive NiV infections in living PBEpC cultures to be monitored by phase-contrast microscopy.
    Matched MeSH terms: Epithelial Cells
  10. A Coxsackievirus B1-mediated nonlytic Extracellular Vesicle-to-cell mechanism of virus transmission and its possible control through modulation of EV release
    Jorfi S, Ansa-Addo EA, Mariniello K, Warde P, Bin Senian AA, Stratton D, et al.
    J Gen Virol, 2023 Sep;104(9).
    PMID: 37665326 DOI: 10.1099/jgv.0.001884
    Like most non-enveloped viruses, CVB1 mainly uses cell lysis to spread. Details of a nonlytic virus transmission remain unclear. Extracellular Vesicles (EVs) transfer biomolecules between cells. We show that CVB1 entry into HeLa cells results in apoptosis and release of CVB1-induced 'medium-sized' EVs (CVB1i-mEVs). These mEVs (100-300 nm) harbour CVB1 as shown by immunoblotting with anti-CVB1-antibody; viral capsids were detected by transmission electron microscopy and RT-PCR revealed CVB1 RNA. The percentage of mEVs released from CVB1-infected HeLa cells harbouring virus was estimated from TEM at 34 %. Inhibition of CVB1i-mEV production, with calpeptin or siRNA knockdown of CAPNS1 in HeLa cells limited spread of CVB1 suggesting these vesicles disseminate CVB1 virions to new host cells by a nonlytic EV-to-cell mechanism. This was confirmed by detecting CVB1 virions inside HeLa cells after co-culture with CVB1i-mEVs; EV release may also prevent apoptosis of infected cells whilst spreading apoptosis to secondary sites of infection.
    Matched MeSH terms: HeLa Cells
  11. Fulltext Ancient forest plants possess cytotoxic properties causing liver cancer HepG2 cell apoptosis
    Yue X, Ling Ma N, Zhong J, Yang H, Chen H, Yang Y, et al.
    Environ Res, 2024 Jan 15;241:117474.
    PMID: 37879390 DOI: 10.1016/j.envres.2023.117474
    Here, we collected 154 plant species in China ancient forests looking for novel efficient bioactive compounds for cancer treatments. We found 600 bioactive phyto-chemicals that induce apoptosis of liver cancer cell in vitro. First, we screen the plant extract's in vitro cytotoxicity inhibition of cancer cell growth using in vitro HepG2 cell lines and MTT cytotoxicity. The results from these initial MTT in vitro cytotoxicity tests show that the most efficient plants towards hepatoma cytoxicity is Cephalotaxus sinensis, mint bush (Elsholtzia stauntonii) and winged spindle tree (Euonymus alatus). We then used in cell-counting kit-8 (CCK-8) to further understand in vivo tumor growth using nude mice and GC-MS and LC-QTOF-MS to analyze the composition of compounds in the extracts. Extracted chemically active molecules analyzed by network pharmacology showed inhibition on the growth of liver cancer cells by acting on multiple gene targets, which is different from the currently used traditional drugs acting on only one target of liver cancer cells. Extracts from Cephalotaxus sinensis, mint bush (Elsholtzia stauntonii) and winged spindle tree (Euonymus alatus) induce apoptosis in hepatoma cancer cell line HepG2 with a killing rate of more than 83% and a tumor size decrease by 62-67% and a killing rate of only 6% of normal hepatocyte LO2. This study highlight efficient candidate species for cancer treatment providing a basis for future development of novel plant-based drugs to help meeting several of the UN SDGs and planetary health.
    Matched MeSH terms: Hep G2 Cells
  12. Inhibition of EREG/ErbB/ERK by Astragaloside IV reversed taxol-resistance of non-small cell lung cancer through attenuation of stemness via TGFβ and Hedgehog signal pathway
    Xiu W, Zhang Y, Tang D, Lee SH, Zeng R, Ye T, et al.
    Cell Oncol (Dordr), 2024 Dec;47(6):2201-2215.
    PMID: 39373858 DOI: 10.1007/s13402-024-00999-7
    PURPOSE: Taxol is the first-line chemo-drug for advanced non-small cell lung cancer (NSCLC), but it frequently causes acquired resistance, which leads to the failure of treatment. Therefore, it is critical to screen and characterize the mechanism of the taxol-resistance reversal agent that could re-sensitize the resistant cancer cells to chemo-drug.

    METHOD: The cell viability, sphere-forming and xenografts assay were used to evaluate the ability of ASIV to reverse taxol-resistance. Immunohistochemistry, cytokine application, small-interfering RNA, small molecule inhibitors, and RNA-seq approaches were applied to characterize the molecular mechanism of inhibition of epiregulin (EREG) and downstream signaling by ASIV to reverse taxol-resistance.

    RESULTS: ASIV reversed taxol resistance through suppression of the stemness-associated genes of spheres in NSCLC. The mechanism exploration revealed that ASIV promoted the K48-linked polyubiquitination of EREG along with degradation. Moreover, EREG could be triggered by chemo-drug treatment. Consequently, EREG bound to the ErbB receptor and activated the ERK signal to regulate the expression of the stemness-associated genes. Inhibition of EREG/ErbB/ERK could reverse the taxol-resistance by inhibiting the stemness-associated genes. Finally, it was observed that TGFβ and Hedgehog signaling were downstream of EREG/ErbB/ERK, which could be targeted using inhibitors to reverse the taxol resistance of NSCLC.

    CONCLUSIONS: These findings revealed that inhibition of EREG by ASIV reversed taxol-resistance through suppression of the stemness of NSCLC via EREG/ErbB/ERK-TGFβ, Hedgehog axis.

    Matched MeSH terms: Neoplastic Stem Cells/drug effects; Neoplastic Stem Cells/metabolism; Neoplastic Stem Cells/pathology
  13. Fulltext Antitumour-promoting and cytotoxic constituents of etlingera elatior
    Habsah M, Ali A, Lajis N, Sukari M, Yap Y, Kikuzaki H, et al.
    Malays J Med Sci, 2005 Jan;12(1):6-12.
    PMID: 22605941
    Phytochemical studies on rhizome of Etlingera elatior have resulted in the isolation of 1,7-bis(4-hydroxyphenyl)-2,4,6-heptatrienone (1), demethoxycurcumin (2), 1,7-bis(4-hydroxyphenyl)-1,4,6-heptatrien-3-one (3), 16-hydroxylabda-8(17),11,13-trien-16,15-olide (4), stigmast-4-en-3-one (5), stigmast-4-ene-3,6-dione (6), stigmast-4-en-6b-ol-3-one (7), 5α,8α-epidioxyergosta-6,22-dien-3β-ol (8). 1 and 4 were new compounds. Compounds 5 and 7 displayed high antitumour-promoting activity. Ethyl acetate extract showed a very significant cytotoxic activity against CEM-SS and MCF-7 cell lines (4 μg/ml and 6.25 μg/ml respectively). The antitumour-promoting activity was determined by EBV-EA assay and cytotoxic activity was determined by MTT assay.
    Matched MeSH terms: MCF-7 Cells
  14. Fulltext Effect of early neonatal exposure to deltamethrin on the purkinje cell number in rat cerebellum
    Asari MA, Abdullah MS, Abdullah S
    Malays J Med Sci, 2008 Jul;15(3):14-21.
    PMID: 22570585 MyJurnal
    Deltamethrin is a widely used insecticide belonging to the class of pyrethroid. Although the neurotoxicity of pyrethroids including deltamethrin is well established, it is still unclear whether exposure to deltamethrin during neonatal period has any deleterious effect on the survival of the Purkinje cells in the cerebellum. In the study, we investigated the total number of Purkinje cells in experimental rats exposed to deltamethrin using a stereological method, the fractionator. Deltamethrin in a dose of 1 mg/kg/day (corresponds to 20% of LD(50) ) was administered through oral gavage to male pups from 2(nd) to 5(th) postnatal day (PND). At PND 21 the animals were sacrificed and their cerebelli were removed. The cerebelli were systematically sampled using the fractionator method and stained with cresyl fast violet. The number of the Purkinje cells was counted for each cerebellum. The results showed that there was no significant difference in the total number of Purkinje cells in the deltamethrin-treated group as compared to the control animals. This suggests that deltamethrin exposure at the current dosage during the neonatal period do not have any significant effect on the survival of the Purkinje cells in the cerebellum.
    Matched MeSH terms: Purkinje Cells
  15. Fulltext Evaluation of Antioxidative and Cytotoxic Activities of Streptomyces pluripotens MUSC 137 Isolated from Mangrove Soil in Malaysia
    Ser HL, Ab Mutalib NS, Yin WF, Chan KG, Goh BH, Lee LH
    Front Microbiol, 2015;6:1398.
    PMID: 26733951 DOI: 10.3389/fmicb.2015.01398
    Streptomyces pluripotens MUSC 137 was isolated from mangrove soil obtained from Tanjung Lumpur, Pahang, Malaysia. We investigated the phylogenetic, genomic, biochemical, and phenotypic characteristics of this strain. Uniquely adapted microorganisms from mangrove habitats have previously yielded compounds of biopharmaceutical interest. In order to examine the bioactivities possessed by the strain, fermentation extract was prepared through solvent extraction method prior to bioactivities screenings. Antioxidant activity was examined via DPPH assay while the cytotoxic effect was assessed by means of examining the activity of the extract against selected human cancer cell lines, namely colon cancer cells (HCT-116, Caco-2, SW480, and HT-29), breast cancer cell (MCF-7), lung cancer cell (A549), prostate cancer cell (DU145), and cervical cancer cell (Ca Ski). The results revealed MUSC 137 possesses significant antioxidant activity and demonstrates cytotoxic effect against several cancer cell lines tested. The results indicated MCF-7 cells were most susceptible to the extract with the lowest IC50 (61.33 ± 17.10 μg/mL), followed by HCT-116 and A549. Additionally, selective index (SI) showed that MUSC 137 extract was less toxic against normal cell lines when compared to MCF-7 and HCT-116 cells. The extract was further subjected to chemical analysis using GC-MS and revealed the presence of deferoxamine and pyrrolizidines related compounds which may account for the antioxidant and cytotoxic properties observed.
    Matched MeSH terms: Caco-2 Cells; HCT116 Cells; MCF-7 Cells
  16. Fulltext Proliferation and stemness preservation of human adipose-derived stem cells by surface-modified in situ TiO₂ nanofibrous surfaces
    Tan AW, Tay L, Chua KH, Ahmad R, Akbar SA, Pingguan-Murphy B
    Int J Nanomedicine, 2014;9:5389-401.
    PMID: 25473278 DOI: 10.2147/IJN.S72659
    Two important criteria of an ideal biomaterial in the field of stem cells research are to regulate the cell proliferation without the loss of its pluripotency and to direct the differentiation into a specific cell lineage when desired. The present study describes the influence of TiO2 nanofibrous surface structures on the regulation of proliferation and stemness preservation of adipose-derived stem cells (ADSCs). TiO2 nanofiber arrays were produced in situ onto Ti-6Al-4V substrate via a thermal oxidation process and the successful fabrication of these nanostructures was confirmed by field emission scanning electron microscopy (FESEM), energy dispersive spectrometer (EDS), X-ray diffractometer (XRD), and contact angle measurement. ADSCs were seeded on two types of Ti-6Al-4V surfaces (TiO2 nanofibers and flat control), and their morphology, proliferation, and stemness expression were analyzed using FESEM, AlamarBlue assay, flow cytometry, and quantitative real-time polymerase chain reaction (qRT-PCR) after 2 weeks of incubation, respectively. The results show that ADSCs exhibit better adhesion and significantly enhanced proliferation on the TiO2 nanofibrous surfaces compared to the flat control surfaces. The greater proliferation ability of TiO2 nanofibrous surfaces was further confirmed by the results of cell cycle assay. More importantly, TiO2 nanofibrous surfaces significantly upregulate the expressions of stemness markers Sox-2, Nanog3, Rex-1, and Nestin. These results demonstrate that TiO2 nanofibrous surfaces can be used to enhance cell adhesion and proliferation while simultaneously maintaining the stemness of ADSCs, thereby representing a promising approach for their potential application in the field of bone tissue engineering as well as regenerative therapies.
    Matched MeSH terms: Cells, Cultured; Pluripotent Stem Cells/drug effects*
  17. Fulltext Oxidative stress-induced premature senescence in Wharton's jelly-derived mesenchymal stem cells
    Choo KB, Tai L, Hymavathee KS, Wong CY, Nguyen PN, Huang CJ, et al.
    Int J Med Sci, 2014;11(11):1201-7.
    PMID: 25249788 DOI: 10.7150/ijms.8356
    On in vitro expansion for therapeutic purposes, the regenerative potentials of mesenchymal stem cells (MSCs) decline and rapidly enter pre-mature senescence probably involving oxidative stress. To develop strategies to prevent or slow down the decline of regenerative potentials in MSC culture, it is important to first address damages caused by oxidative stress-induced premature senescence (OSIPS). However, most existing OSIPS study models involve either long-term culture to achieve growth arrest or immediate growth arrest post oxidative agent treatment and are unsuitable for post-induction studies.
    Matched MeSH terms: Mesenchymal Stromal Cells/cytology*; Mesenchymal Stromal Cells/drug effects
  18. Fulltext Role of rutin on nitric oxide synthesis in human umbilical vein endothelial cells
    Ugusman A, Zakaria Z, Chua KH, Nordin NA, Abdullah Mahdy Z
    ScientificWorldJournal, 2014;2014:169370.
    PMID: 25093198 DOI: 10.1155/2014/169370
    Nitric oxide (NO), produced by endothelial nitric oxide synthase (eNOS), is a major antiatherogenic factor in the blood vessel. Oxidative stress plays an important role in the pathogenesis of various cardiovascular diseases, including atherosclerosis. Decreased availability of endothelial NO promotes the progression of endothelial dysfunction and atherosclerosis. Rutin is a flavonoid with multiple cardiovascular protective effects. This study aimed to investigate the effects of rutin on eNOS and NO production in cultured human umbilical vein endothelial cells (HUVEC). HUVEC were divided into four groups: control; oxidative stress induction with 180 μM H₂O₂; treatment with 300 μM rutin; and concomitant induction with rutin and H₂O₂ for 24 hours. HUVEC treated with rutin produced higher amount of NO compared to control (P < 0.01). In the oxidative stress-induced HUVEC, rutin successfully induced cells' NO production (P < 0.01). Rutin promoted NO production in HUVEC by inducing eNOS gene expression (P < 0.05), eNOS protein synthesis (P < 0.01), and eNOS activity (P < 0.05). Treatment with rutin also led to increased gene and protein expression of basic fibroblast growth factor (bFGF) in HUVEC. Therefore, upregulation of eNOS expression by rutin may be mediated by bFGF. The results showed that rutin may improve endothelial function by augmenting NO production in human endothelial cells.
    Matched MeSH terms: Human Umbilical Vein Endothelial Cells/drug effects*; Human Umbilical Vein Endothelial Cells/metabolism*
  19. Assessment of genotoxic and molecular mechanisms of cancer risk in smoking and smokeless tobacco users
    Chandirasekar R, Kumar BL, Sasikala K, Jayakumar R, Suresh K, Venkatesan R, et al.
    Mutat Res Genet Toxicol Environ Mutagen, 2014 Jun;767:21-7.
    PMID: 24769293 DOI: 10.1016/j.mrgentox.2014.04.007
    Inexpensive forms of tobacco are widely used in developing countries such as India. We have evaluated genotoxicity endpoints (chromosome aberrations, micronucleus frequency, comet assay) and polymorphisms of the XRCC1 and p53 genes among smokers and smokeless tobacco (SLT) users in rural Tamilnadu, South India. Cytogenetic, DNA damage and SNP analyses were performed on peripheral blood samples; micronucleus frequency was measured in peripheral blood and buccal mucosa exfoliated cells. Both categories of tobacco users had elevated levels of genotoxic damage. SNP analysis of tobacco users revealed that 17% carry the XRCC1 gln399gln genotype and 19% carry the p53 pro72pro genotype. Both genotypes are associated with increased risk of cancer.
    Matched MeSH terms: Blood Cells/metabolism; Blood Cells/pathology
  20. Fulltext Interleukin-6 and intercellular cell adhesion molecule-1 expression remains elevated in revived live endothelial cells following spaceflight
    Muid S, Froemming GR, Ali AM, Nawawi H
    Malays J Pathol, 2013 Dec;35(2):165-76.
    PMID: 24362480 MyJurnal
    The effects of spaceflight on cardiovascular health are not necessarily seen immediately after astronauts have returned but can be delayed. It is important to investigate the long term effects of spaceflight on protein and gene expression of inflammation and endothelial activation as a predictor for the development of atherosclerosis and potential cardiovascular problems. The objectives of this study were to investigate the (a) protein and gene expression of inflammation and endothelial activation, (b) expression of nuclear factor kappa B (NFκB), signal transducer and activator of transcription-3 (STAT-3) and endothelial nitric oxide synthase (eNOS) in human umbilical vein endothelial cells (HUVEC) 3 months post-space flight travel compared to ground controls. HUVEC cultured on microcarriers in fluid processing apparatus were flown to the International Space Station (ISS) by the Soyuz TMA-11 rocket. After landing, the cells were detached from microcarriers and recultured in T-25 cm(2) culture flasks (Revived HUVEC). Soluble protein expression of IL-6, TNF-α, ICAM-1, VCAM-1 and e-selectin were measured by ELISA. Gene expression of these markers and in addition NFκB, STAT-3 and eNOS were measured. Spaceflight induced IL-6 and ICAM-1 remain elevated even after 3 months post spaceflight travel and this is mediated via STAT-3 pathway. The downregulation of eNOS expression in revived HUVEC cells suggests a reduced protection of the cells and the surrounding vessels against future insults that may lead to atherosclerosis. It would be crucial to explore preventive measures, in relation to atherosclerosis and its related complications.
    Matched MeSH terms: Cells, Cultured; Endothelial Cells/metabolism*
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