Displaying publications 1501 - 1520 of 3311 in total

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  1. Fakai MI, Abd Malek SN, Karsani SA
    Life Sci, 2019 Mar 01;220:186-193.
    PMID: 30682342 DOI: 10.1016/j.lfs.2019.01.029
    AIMS: Chalepin, a naturally occurring compound isolated from Ruta angustifolia have been shown to exert a promising anticancer activity through various mechanisms. Hence, the need to investigate the apoptotic inducing ability of chalepin in MCF7 cells by various detection assays.

    MATERIALS AND METHODS: Cytotoxicity screening of chalepin against MCF7 cells was conducted using SRB assay. Apoptosis induction was examined by established morphological and biochemical assays including phase contrast and Hoechst/PI staining fluorescence microscope. Similarly, Annexin-V/FITC and TUNEL assays were conducted using flow cytometry whereas caspase-3 activity was evaluated using microplate reader.

    KEY FINDINGS: The result indicates remarkable cytotoxic activity against MCF7 cells, whereas it shows moderate cytotoxic activity against MDA-MB231 cells. Interestingly, chalepin did not present any toxicity against MRC5 normal cell line. Morphological examination using both phase contrast and fluorescence microscope displays typical apoptotic features such as membrane blebbing, DNA fragmentation, chromatin condensation and apoptotic bodies' formation following chalepin treatment against MCF7 cells at different concentration for 48 h. Apoptosis induction is significantly associated with externalisation of phosphatidylserine, and DNA fragmentation in MCF7 cells chalepin treated cells when compared with control. The protein expressions of caspase-8, 9 and cleaved PARP1 were upregulated which correlated well with increased caspase-3 activity.

    SIGNIFICANCE: From our recent findings, chalepin was able to induced apoptosis in MCF7 cells and therefore, could be evaluated further as a potential source of anticancer agent for cancer treatment such as breast cancer.

    Matched MeSH terms: MCF-7 Cells/drug effects
  2. Nordin F, Idris MRM, Mahdy ZA, Wahid SFA
    BMC Pregnancy Childbirth, 2020 Jul 10;20(1):399.
    PMID: 32650736 DOI: 10.1186/s12884-020-03084-7
    BACKGROUND: Umbilical cord blood (UCB) has been proposed as the potential source of haematopoietic stem cells (HSC) for allogeneic transplantation. However, few studies have shown that a common disease in pregnancy such as preeclampsia would affect the quality of UCB-HSC. Total nucleated cell count (TNC) is an important parameter that can be used to predict engraftment including UCB banking. Colony forming unit (CFU) assay is widely used as an indicator to predict the success of engraftment, since direct quantitative assay for HSC proliferation is unavailable. The aim of this study is to investigate the effects of preeclampsia in pregnancy on the stemness and differentiation potency of UCB-HSC.

    METHODS: Mononuclear cells (MNC) were isolated from UCB and further enriched for CD34+ cells using immune-magnetic method followed by CFU assay. A panel of HSC markers including differentiated haematopoietic markers were used to confirm the differentiation ability of UCB-HSC by flow cytometry analysis.

    RESULTS/ DISCUSSION: The HSC progenitor's colonies from the preeclampsia group were significantly lower compared to the control. This correlates with the low UCB volume, TNC and CD34+ cells count. In addition, the UCB-enriched CD34+ population were lymphoid progenitors and capable to differentiate into natural killer cells and T-lymphocytes.

    CONCLUSION: These findings should be taken into consideration when selecting UCB from preeclamptic mothers for banking and predicting successful treatment related to UCB transplant.

    Matched MeSH terms: Hematopoietic Stem Cells/cytology*
  3. Mohammad Salih PA
    J Glaucoma, 2012 Jan;21(1):41-4.
    PMID: 21173707 DOI: 10.1097/IJG.0b013e3181fc8053
    To investigate the influence of myopia on peripapillary retinal nerve fiber layer (RNFL) thickness using Cirrus optical coherence tomography (OCT) in normal eyes.
    Matched MeSH terms: Retinal Ganglion Cells/pathology*
  4. Yusoff FM, Kajikawa M, Takaeko Y, Kishimoto S, Hashimoto H, Maruhashi T, et al.
    Sci Rep, 2020 11 16;10(1):19891.
    PMID: 33199760 DOI: 10.1038/s41598-020-76886-6
    Cell therapy using intramuscular injections of autologous bone-marrow mononuclear cells (BM-MNCs) improves clinical symptoms and can prevent limb amputation in atherosclerotic peripheral arterial disease (PAD) patients with critical limb ischemia (CLI). The purpose of this study was to evaluate the effects of the number of implanted BM-MNCs on clinical outcomes in atherosclerotic PAD patients with CLI who underwent cell therapy. This study was a retrospective observational study with median follow-up period of 13.5 years (range, 6.8-15.5 years) from BM-MNC implantation procedure. The mean number of implanted cells was 1.2 ± 0.7 × 109 per limb. There was no significant difference in number of BM-MNCs implanted between the no major amputation group and major amputation group (1.1 ± 0.7 × 109 vs. 1.5 ± 0.8 × 109 per limb, P = 0.138). There was also no significant difference in number of BM-MNCs implanted between the no death group and death group (1.5 ± 0.9 × 109 vs. 1.8 ± 0.8 × 109 per patient, P = 0.404). Differences in the number of BM-MNCs (mean number, 1.2 ± 0.7 × 109 per limb) for cell therapy did not alter the major amputation-free survival rate or mortality rate in atherosclerotic PAD patients with CLI. A large number of BM-MNCs will not improve limb salvage outcome or mortality.
    Matched MeSH terms: Bone Marrow Cells/cytology*
  5. Veligeti R, Madhu RB, Anireddy J, Pasupuleti VR, Avula VKR, Ethiraj KS, et al.
    Sci Rep, 2020 11 26;10(1):20720.
    PMID: 33244007 DOI: 10.1038/s41598-020-77590-1
    Acridone based synthetic and natural products with inherent anticancer activity advancing the research and generating a large number of structurally diversified compounds. In this sequence we have designed, synthesized a series of tetracyclic acridones with amide framework viz., 3-(alkyloyl/ aryloyl/ heteroaryloyl/ heteroaryl)-2,3-dihydropyrazino[3,2,1-de]acridin-7(1H)-ones and screened for their in vitro anti-cancer activity. The in vitro study revealed that compounds with cyclopropyl-acetyl, benzoyl, p-hydroxybenzoyl, p-(trifluoromethyl)benzoyl, p-fluorobenzoyl, m-fluorobenzoyl, picolinoyl, 6-methylpicolinoyl and 3-nicotinoyl groups are active against HT29, MDAMB231 and HEK293T cancer cell lines. The molecular docking studies performed for them against 4N5Y, HT29 and 2VWD revealed the potential ligand-protein binding interactions among the neutral aminoacid of the enzymes and carbonyl groups of the title compounds with a binding energy ranging from - 8.1394 to - 6.9915 kcal/mol. In addition, the BSA protein binding assay performed for them has confirmed their interaction with target proteins through strong binding to BSA macromolecule. The additional studies like ADMET, QSAR, bioactivity scores, drug properties and toxicity risks ascertained them as newer drug candidates. This study had added a new collection of piperazino fused acridone derivatives to the existing array of other nitrogen heterocyclic fused acridone derivatives as anticancer agents.
    Matched MeSH terms: HT29 Cells; HEK293 Cells
  6. Panahi M, Rahimi B, Rahimi G, Yew Low T, Saraygord-Afshari N, Alizadeh E
    J Cell Physiol, 2020 10;235(10):6462-6495.
    PMID: 32239727 DOI: 10.1002/jcp.29660
    Mesenchymal stem cells (MSCs) are earmarked as perfect candidates for cell therapy and tissue engineering due to their capacity to differentiate into different cell types. However, their potential for application in regenerative medicine declines when the levels of the reactive oxygen and nitrogen species (RONS) increase from the physiological levels, a phenomenon which is at least inevitable in ex vivo cultures and air-exposed damaged tissues. Increased levels of RONS can alter the patterns of osteogenic and adipogenic differentiation and inhibit proliferation, as well. Besides, oxidative stress enhances senescence and cell death, thus lowering the success rates of the MSC engraftment. Hence, in this review, we have selected some representatives of antioxidants and newly emerged nano antioxidants in three main categories, including chemical compounds, biometabolites, and protein precursors/proteins, which are proved to be effective in the treatment of MSCs. We will focus on how antioxidants can be applied to optimize the clinical usage of the MSCs and their associated signaling pathways. We have also reviewed several paralleled properties of some antioxidants and nano antioxidants which can be simultaneously used in real-time imaging, scaffolding techniques, and other applications in addition to their primary antioxidative function.
    Matched MeSH terms: Mesenchymal Stromal Cells/drug effects*
  7. Lee HM, Sia APE, Li L, Sathasivam HP, Chan MSA, Rajadurai P, et al.
    Sci Rep, 2020 04 09;10(1):6115.
    PMID: 32273550 DOI: 10.1038/s41598-020-63150-0
    Nasopharyngeal carcinoma (NPC) is a highly metastatic cancer that is consistently associated with Epstein-Barr virus (EBV) infection. In this study, we identify for the first time a role for monoamine oxidase A (MAOA) in NPC. MAOA is a mitochondrial enzyme that catalyzes oxidative deamination of neurotransmitters and dietary amines. Depending on the cancer type, MAOA can either have a tumour-promoting or tumour-suppressive role. We show that MAOA is down-regulated in primary NPC tissues and its down-regulation enhances the migration of NPC cells. In addition, we found that EBV infection can down-regulate MAOA expression in both pre-malignant and malignant nasopharyngeal epithelial (NPE) cells. We further demonstrate that MAOA is down-regulated as a result of IL-6/IL-6R/STAT3 signalling and epigenetic mechanisms, effects that might be attributed to EBV infection in NPE cells. Taken together, our data point to a central role for EBV in mediating the tumour suppressive effects of MAOA and that loss of MAOA could be an important step in the pathogenesis of NPC.
    Matched MeSH terms: Epithelial Cells/metabolism
  8. Basu Baul TS, Dutta D, Duthie A, Prasad R, Rana NK, Koch B, et al.
    J Inorg Biochem, 2017 08;173:79-92.
    PMID: 28505480 DOI: 10.1016/j.jinorgbio.2017.04.020
    The cytotoxic potency of a series of triphenyltin(IV) compounds of general composition [Ph3Sn(Ln)] (1-6) has been probed in vitro employing MDA-MB-231 (human breast cancer) and HeLa (human cervical cancer) cell lines, where Ln=L1-3; isomeric 2/3/4-{(E)-2-[4-(dimethylamino)phenyl]diazenyl}benzoates and L4-6are their corresponding isoelectronic imino analogues 2/3/4-[(E)-{[4-(dimethylamino)phenyl]methylidene}amino]benzoates. Compounds 1-6 have been characterized by elemental analysis and their spectroscopic properties were studied using IR and NMR (1H,13C,119Sn) techniques. The molecular structures of a pro-ligand 2-[(E)-{[4-(dimethylamino)phenyl]methylidene}amino]benzoic acid (HL4) and two representative molecules, Ph3Sn(L2) 2 and Ph3Sn(L5) 5, have been determined by X-ray crystallography. Structural analyses of 2 and 5 revealed distorted tetrahedral geometries within C3O donor sets owing to monodentate modes of coordination of the respective carboxylate ligands, close intramolecular Sn…O(carbonyl) interactions notwithstanding. Cytotoxic studies in vitro in MDA-MB-231 and HeLa cell lines revealed high activity, in sub-micromolar range, for all investigated compounds. Among these, 1 and 3 exhibited potent cytotoxicity most effectively towards MDA-MB-231 cells with a IC50value of 1.19 and 1.44μM, respectively, whereas 5 showed remarkable activity towards HeLa cells with a IC50value of 0.88μM, yet the series of compounds had minimal cytotoxic effect on normal HEK 293 (human embryonic kidney) cell line. The underlying investigation suggested that the compounds exert potent antitumor effect by elevating intracellular reactive oxygen species generation and cause delay in cell cycle by inhibiting cells at G2/M phase. The results presented herein suggest further development of this class of triphenyltin(IV) compounds-based drugs as potential anti-cancer therapies should be pursued.
    Matched MeSH terms: HeLa Cells; HEK293 Cells
  9. Musa M, Ouaret D, Bodmer WF
    Anticancer Res, 2020 Nov;40(11):6063-6073.
    PMID: 33109544 DOI: 10.21873/anticanres.14627
    BACKGROUND/AIM: Interactions between colorectal cancer (CRC) cells and myofibroblasts govern many processes such as cell growth, migration, invasion and differentiation, and contribute to CRC progression. Robust experimental tests are needed to investigate the nature of these interactions for future anticancer studies. The purpose of the study was to design and validate in vitro assays for studying the communication between myofibroblasts and CRC epithelial cell lines.

    MATERIALS AND METHODS: The influence of co-culture of myofibroblasts and CRC cell lines is discussed using various in vitro assays including direct co-culture, transwell assays, Matrigel-based differentiation and cell invasion experiments.

    RESULTS: The results from these in vitro assays clearly demonstrated various aspects of the crosstalk between myofibroblasts and CRC cell lines, which include cell growth, differentiation, migration and invasion.

    CONCLUSION: The reported in vitro assays provide a basis for investigating the factors that control the myofibroblast-epithelial cell interactions in CRC in vivo.

    Matched MeSH terms: Epithelial Cells/drug effects
  10. Yeo Y, Tan JBL, Lim LW, Tan KO, Heng BC, Lim WL
    Biomed Res Int, 2019;2019:3126376.
    PMID: 33204680 DOI: 10.1155/2019/3126376
    In the biomedical field, there is growing interest in using human stem cell-derived neurons as in vitro models for pharmacological and toxicological screening of bioactive compounds extracted from natural products. Lignosus rhinocerus (Tiger Milk Mushroom) is used by indigenous communities in Malaysia as a traditional medicine to treat various diseases. The sclerotium of L. rhinocerus has been reported to have medicinal properties, including various bioactivities such as neuritogenic, anti-inflammatory, and anticancer effects. This study aims to investigate the neuroprotective activities of L. rhinocerus sclerotial extracts. Human embryonic stem cell (hESC)-derived neural lineages exposed to the synthetic glucocorticoid, dexamethasone (DEX), were used as the in vitro models. Excess glucocorticoids have been shown to adversely affect fetal brain development and impair differentiation of neural progenitor cells. Screening of different L. rhinocerus sclerotial extracts and DEX on the hESC-derived neural lineages was conducted using cell viability and neurite outgrowth assays. The neuroprotective effects of L. rhinocerus sclerotial extracts against DEX were further evaluated using apoptosis assays and Western blot analysis. Hot aqueous and methanol extracts of L. rhinocerus sclerotium promoted neurite outgrowth of hESC-derived neural stem cells (NSCs) with negligible cytotoxicity. Treatment with DEX decreased viability of NSCs by inducing apoptosis. Coincubation of L. rhinocerus methanol extract with DEX attenuated the DEX-induced apoptosis and reduction in phospho-Akt (pAkt) level in NSCs. These results suggest the involvement of Akt signaling in the neuroprotection of L. rhinocerus methanol extract against DEX-induced apoptosis in NSCs. Methanol extract of L. rhinocerus sclerotium exhibited potential neuroprotective activities against DEX-induced toxicity in hESC-derived NSCs. This study thus validates the use of human stem cell-derived neural lineages as potential in vitro models for screening of natural products with neuroprotective properties.
    Matched MeSH terms: Human Embryonic Stem Cells*
  11. Ayakannu R, Abdullah NA, Radhakrishnan AK, Lechimi Raj V, Liam CK
    Hum Immunol, 2019 Sep;80(9):755-763.
    PMID: 31054782 DOI: 10.1016/j.humimm.2019.04.018
    Asthma is a complex disorder involving immunologic, environmental, genetic and other factors. Today, asthma is the most common disease encountered in clinical medicine in both children and adults worldwide. Asthma is characterized by increased responsiveness of the tracheobronchial tree resulting in chronic swelling and inflammation of the airways recognized to be controlled by the T-helper 2 (Th2) lymphocytes, which secrete cytokines to increase the production of IgE by B cells. There are many cytokines implicated in the development of the chronic inflammatory processes that are often observed in asthma. Ultimately, these cytokines cause the release of mediators such as histamine and leukotrienes (LT), which in turn promote airway remodeling, bronchial hyperresponsiveness and bronchoconstriction. The CD4+ T-lymphocytes from the airways of asthmatics express a panel of cytokines that represent the Th2 cells. The knowledge derived from numerous experimental and clinical studies have allowed physicians and scientists to understand the normal functions of these cytokines and their roles in the pathogenesis of asthma. The main focus of this review is to accentuate the relationship between various cytokines implicated in human asthma. However, some key findings from animal models will be highlighted to support the discoveries from clinical studies.
    Matched MeSH terms: Th2 Cells/immunology
  12. Gunawardena TNA, Masoudian Z, Rahman MT, Ramasamy TS, Ramanathan A, Abu Kasim NH
    PLoS One, 2019;14(5):e0216003.
    PMID: 31042749 DOI: 10.1371/journal.pone.0216003
    Alopecia is a clinical condition caused by excessive hair loss which may result in baldness, the causes of which still remain elusive. Conditioned media (CM) from stem cells shows promise in regenerative medicine. Our aim was to evaluate the potential CM of dental pulp stem cells obtained from human deciduous teeth (SHED-CM) to stimulate hair growth under in vitro and in vivo conditions. SHED and hair follicle stem cells (HFSCs) (n = 3) were cultured in media combinations; i) STK2, ii) DMEM-KO+10% FBS, iii) STK2+2% FBS and profiled for the presence of positive hair growth-regulatory paracrine factors; SDF-1, HGF, VEGF-A, PDGF-BB and negative hair growth-regulatory paracrine factors; IL-1α, IL-1β, TGF-β, bFGF, TNF-α, and BDNF. The potential of CM from both cell sources to stimulate hair growth was evaluated based on the paracrine profile and measured dynamics of hair growth under in vitro conditions. The administration of CM media to telogen-staged synchronized 7-week old C3H/HeN female mice was carried out to study the potential of the CM to stimulate hair growth in vivo. SHED and HFSCs cultured in STK2 based media showed a shorter population doubling time, higher viability and better maintenance of MSC characteristics in comparison to cells cultured in DMEM-KO media. STK2 based CM contained only two negative hair growth-regulatory factors; TNF-α, IL-1 while DMEM-KO CM contained all negative hair growth-regulatory factors. The in vitro study confirmed that treatment with STK2 based media CM from passage 3 SHED and HFSCs resulted in a significantly higher number of anagen-staged hair follicles (p<0.05) and a significantly lower number of telogen-staged hair follicles (p<0.05). Administration of SHED-CM to C3H/HeN mice resulted in a significantly faster stimulation of hair growth in comparison to HFSC-CM (p<0.05), while the duration taken for complete hair coverage was similar for both CM sources. Thus, SHED-CM carries the potential to stimulate hair growth which can be used as a treatment tool for alopecia.
    Matched MeSH terms: Adult Stem Cells/metabolism
  13. Paudel KR, Wadhwa R, Mehta M, Chellappan DK, Hansbro PM, Dua K
    Toxicol In Vitro, 2020 Oct;68:104961.
    PMID: 32771431 DOI: 10.1016/j.tiv.2020.104961
    Airway inflammation and infections are the primary causes of damage in the airway epithelium, that lead to hypersecretion of mucus and airway hyper-responsiveness. The role of reactive oxygen species (ROS) and their components in the pathophysiological mechanisms of airway inflammation have been well-studied and emphasized for the past several decades. Rutin, a potent bioflavonoid, is well-known for its antioxidant, anti-inflammatory, especially in bronchial inflammation. However, poor solubility and rapid metabolism have led to its low bioavailability in biological systems, and hence limit its application. The present study aims to investigate the beneficial effects of rutin-loaded liquid crystalline nanoparticles (LCNs) against lipopolysaccharide (LPS) induced oxidative damage in human bronchial epithelial cell line (BEAS-2-B) cells in vitro. LPS was used to stimulate BEAS-2-B cells, causing the generation of nitric oxide (NO) and other reactive oxygen species (ROS) that had led to cellular apoptosis. The levels of NO and ROS were detected by, Griess reagent kit and dichlorodihydrofluorescein diacetate (DCFH-DA) respectively, whereas, cell apoptosis was studied by Annexin V-FITC and PI staining. The findings revealed that rutin-loaded LCNs significantly reduced NO, ROS levels and prevented apoptosis in BEAS-2B cells. The observations and findings provide a mechanistic understanding of the effectiveness of rutin-loaded LCNs in protecting the bronchial cells against airway inflammation, thus possessing a promising therapeutic option for the management of airway diseases.
    Matched MeSH terms: Epithelial Cells/drug effects*
  14. Mohd-Ali B, Chen LY
    Cont Lens Anterior Eye, 2021 02;44(1):72-75.
    PMID: 32624364 DOI: 10.1016/j.clae.2020.06.007
    PURPOSE: To analyse and compare the alterations in corneal endothelium morphology induced by different materials and durations of wearing soft contact lenses (CL) among young adults living in Kuala Lumpur.

    METHODS: Healthy soft CL wearers were invited to participate in this study. Visual acuity (VA) was measured using the Snellen chart, and subjective refraction was performed using cross-cylinder technique. Standard ocular assessments were conducted using a slit lamp biomicroscope and morphology of corneal endothelial cells (endothelial cell density, ECD, coefficient variation, COV, hexagonality, HEX and central corneal thickness, CCT) were evaluated using a non-contact specular microscope. Statistical analysis was conducted using ANOVA and data from the right eye only is included.

    RESULTS: A total of 72 subjects (32 SiHy and 40 HCL wearers) and 24 non-CL wearers (control) participated in this study. The gender distribution for study subjects was 13 males and 59 females, with a mean age 22.15 ± 1.84 years old. The mean refraction was -1.86 ± 1.25DS. The duration of wearing CL ranged from 1 to 9 years. Subjects were later divided into 2 groups following duration of CL wear: Group 1 (<5 years) and Group 2 (≥5 years) for analysis purposes. Statistical analysis showed significant alterations in ECD, COV and HEX of CL wearers (p 

    Matched MeSH terms: Endothelial Cells/pathology
  15. Kumari M, Tahlan S, Narasimhan B, Ramasamy K, Lim SM, Shah SAA, et al.
    BMC Chem, 2021 Jan 21;15(1):5.
    PMID: 33478538 DOI: 10.1186/s13065-020-00717-y
    BACKGROUND: Triazole is an important heterocyclic moiety that occupies a unique position in heterocyclic chemistry, due to its large number of biological activities. It exists in two isomeric forms i.e. 1,2,4-triazole and 1,2,3-triazole and is used as core molecule for the design and synthesis of many medicinal compounds. 1,2,4-Triazole possess broad spectrum of therapeutically interesting drug candidates such as analgesic, antiseptic, antimicrobial, antioxidant, anti-urease, anti-inflammatory, diuretics, anticancer, anticonvulsant, antidiabetic and antimigraine agents.

    METHODS: The structures of all synthesized compounds were characterized by physicochemical properties and spectral means (IR and NMR). The synthesized compounds were evaluated for their in vitro antimicrobial activity against Gram-positive (B. subtilis), Gram-negative (P. aeruginosa and E. coli) bacterial and fungal (C. albicans and A. niger) strains by tube dilution method using ciprofloxacin, amoxicillin and fluconazole as standards. In-vitro antioxidant and anti-urease screening was done by DPPH assay and indophenol method, respectively. The in-vitro anticancer evaluation was carried out against MCF-7 and HCT116 cancer cell lines using 5-FU as standards.

    RESULTS, DISCUSSION AND CONCLUSION: The biological screening results reveal that the compounds T5 (MICBS, EC = 24.7 µM, MICPA, CA = 12.3 µM) and T17 (MICAN = 27.1 µM) exhibited potent antimicrobial activity as comparable to standards ciprofloxacin, amoxicillin (MICCipro = 18.1 µM, MICAmo = 17.1 µM) and fluconazole (MICFlu = 20.4 µM), respectively. The antioxidant evaluation showed that compounds T2 (IC50 = 34.83 µg/ml) and T3 (IC50 = 34.38 µg/ml) showed significant antioxidant activity and comparable to ascorbic acid (IC50 = 35.44 µg/ml). Compounds T3 (IC50 = 54.01 µg/ml) was the most potent urease inhibitor amongst the synthesized compounds and compared to standard thiourea (IC50 = 54.25 µg/ml). The most potent anticancer activity was shown by compounds T2 (IC50 = 3.84 μM) and T7 (IC50 = 3.25 μM) against HCT116 cell lines as compared to standard 5-FU (IC50 = 25.36 μM).

    Matched MeSH terms: HCT116 Cells; MCF-7 Cells
  16. Lee C, Yiau KXS, Lee LJ, Chong PP, Chang KM, Abdullah M
    Malays J Pathol, 2019 Dec;41(3):313-326.
    PMID: 31901916
    INTRODUCTION: Quantitative polymerase chain reaction (qPCR) is commonly used in the investigation of acute myeloid leukaemias (AML). Stable reference genes (RG) are essential for accurate and reliable reporting but no standard method for selection has been endorsed.

    MATERIALS AND METHODS: We evaluated simple statistics and published model-based approaches. Multiplex-qPCR was conducted to determine the expression of 24 candidate RG in AMLs (N=9). Singleplex-qPCR was carried out on selected RG (SRP14, B2M and ATP5B) and genes of interest in AML (N=15) and healthy controls, HC (N=12).

    RESULTS: RG expression levels in AML samples were highly variable and coefficient of variance (CV) ranged from 0.37% to 10.17%. Analysis using GeNorm and Normfinder listed different orders of most stable genes but the top seven (ACTB, UBE2D2, B2M, NF45, RPL37A, GK, QARS) were the same. In singleplex-qPCR, SRP14 maintained the lowest CV in AML samples. B2M, one of most stable reference genes in AML, was expressed near significantly different in AML and HC. GeNorm selected ATP5B+SRP14 while Normfinder chose SRP14+B2M as the best two RG in combination. The median expressions of combined RG genes in AML compared to HC were less significantly different than individually implying smaller expression variation after combination. Genes of interest normalised with RG in combination or individually, displayed significantly different expression patterns.

    CONCLUSIONS: The selection of best reference gene in qPCR must consider all sample sets. Model-based approaches are important in large candidate gene analysis. This study showed combination of RG SRP14+B2M was the most suitable normalisation factor for qPCR analysis of AML and healthy individuals.

    Matched MeSH terms: Bone Marrow Cells/cytology
  17. Hitora Y, Takada K, Ise Y, Woo SP, Inoue S, Mori N, et al.
    Bioorg Med Chem, 2020 01 15;28(2):115233.
    PMID: 31848114 DOI: 10.1016/j.bmc.2019.115233
    New sesquiterpene quinones, metachromins X (1) and Y (2), together with the known metachromins C (3), J (4), and T (5), were isolated as inhibitors of cell cycle progression in the HeLa/Fucci2 cells. The structure of 1 was assigned by spectroscopic data and confirmed by a total synthesis. The planar structure of 2 was determined by interpretation of spectroscopic data, whereas its absolute configuration was analyzed by a combination of chiral HPLC and CD spectroscopy. Metachromins X (1) and C (3) arrested the cell cycle progression of HeLa/Fucci2 cells at S/G2/M phase.
    Matched MeSH terms: HeLa Cells; Tumor Cells, Cultured
  18. Sivasothy Y, Hadi AH, Mohamad K, Leong KH, Ibrahim H, Sulaiman SF, et al.
    Bioorg Med Chem Lett, 2012 Jun 1;22(11):3831-6.
    PMID: 22546674 DOI: 10.1016/j.bmcl.2012.02.064
    The rhizomes of Zingiber spectabile yielded a new dimeric flavonol glycoside for which the name kaempferol-3-O-(4″-O-acetyl)-α-L-rhamnopyranoside-(I-6,II-8)-kaempferol-3-O-(4″-O-acetyl)-α-L-rhamnopyranoside; spectaflavoside A (1) was proposed, along with kaempferol and its four acetylrhamnosides (2-6), demethoxycurcumin (7) and curcumin (8). The structure of spectaflavoside A was elucidated by spectroscopic methods including, 1D and 2D NMR techniques. This is the first report on the occurrence of a dimeric flavonol glycoside in the Zingiberaceae and the second in nature. Spectaflavoside A was found to be a potent iron chelating agent.
    Matched MeSH terms: HT29 Cells; Hep G2 Cells
  19. Loughland JR, Woodberry T, Oyong D, Piera KA, Amante FH, Barber BE, et al.
    Malar J, 2021 Feb 16;20(1):97.
    PMID: 33593383 DOI: 10.1186/s12936-021-03642-0
    BACKGROUND: Plasmodium falciparum malaria increases plasma levels of the cytokine Fms-like tyrosine kinase 3 ligand (Flt3L), a haematopoietic factor associated with dendritic cell (DC) expansion. It is unknown if the zoonotic parasite Plasmodium knowlesi impacts Flt3L or DC in human malaria. This study investigated circulating DC and Flt3L associations in adult malaria and in submicroscopic experimental infection.

    METHODS: Plasma Flt3L concentration and blood CD141+ DC, CD1c+ DC and plasmacytoid DC (pDC) numbers were assessed in (i) volunteers experimentally infected with P. falciparum and in Malaysian patients with uncomplicated (ii) P. falciparum or (iii) P. knowlesi malaria.

    RESULTS: Plasmodium knowlesi caused a decline in all circulating DC subsets in adults with malaria. Plasma Flt3L was elevated in acute P. falciparum and P. knowlesi malaria with no increase in a subclinical experimental infection. Circulating CD141+ DCs, CD1c+ DCs and pDCs declined in all adults tested, for the first time extending the finding of DC subset decline in acute malaria to the zoonotic parasite P. knowlesi.

    CONCLUSIONS: In adults, submicroscopic Plasmodium infection causes no change in plasma Flt3L but does reduce circulating DCs. Plasma Flt3L concentrations increase in acute malaria, yet this increase is insufficient to restore or expand circulating CD141+ DCs, CD1c+ DCs or pDCs. These data imply that haematopoietic factors, yet to be identified and not Flt3L, involved in the sensing/maintenance of circulating DC are impacted by malaria and a submicroscopic infection. The zoonotic P. knowlesi is similar to other Plasmodium spp in compromising DC in adult malaria.

    Matched MeSH terms: Dendritic Cells/metabolism*
  20. Yasmin AR, Omar AR, Farhanah MI, Hiscox AJ, Yeap SK
    Avian Dis, 2019 06 01;63(2):275-288.
    PMID: 31251527 DOI: 10.1637/11936-072418-Reg.1
    Chicken dendritic cells (DCs) have been demonstrated to be susceptible to infectious bursal disease virus (IBDV), a causative agent of acute and immunosuppressed disease in young chicks known as infectious bursal disease. Further functional characterization of IBDV-infected DCs of chickens is required to provide a better understanding on the influence of the virus on chicken bone marrow-derived dendritic cells (BM-DCs) following very virulent (vv) IBDV infection. Membrane proteins of BM-DCs were extracted and the proteins were further denatured and reduced before performing labeling with isobaric tags for relative and absolute quantitation. The differential expression protein profiles were identified and quantified using liquid chromatography coupled with tandem mass spectrometry, and later validated using flow cytometry and real-time reverse transcriptase PCR. The analysis has identified 134 differentially regulated proteins from a total of 283 proteins (cutoff values of ≤0.67, ≥1.5, and ProtScore >1.3 at 95% confidence interval), which produced high-yield membrane fractions. The entry of vvIBDV into the plasma membrane of BM-DCs was observed at 3 hr postinfection by the disruption of several important protein molecule functions, namely apoptosis, RNA/DNA/protein synthesis, and transport and cellular organization, without the activation of proteins associated with signaling. At the later stage of infection, vvIBDV induced expression of several proteins, namely CD200 receptor 1-A, integrin alpha-5, HSP-90, cathepsin, lysosomal-associated membrane protein, and Ras-related proteins, which play crucial roles in signaling, apoptosis, stress response, and antigen processing as well as in secretion of danger-associated proteins. These findings collectively indicated that the chicken DCs are expressing various receptors regarded as potential targets for pathogen interaction during viral infection. Therefore, fundamental study of the interaction of DCs and IBDV will provide valuable information in understanding the role of professional antigen-presenting cells in chickens and their molecular interactions during IBDV infection and vaccination.
    Matched MeSH terms: Dendritic Cells/immunology*
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