Displaying publications 1 - 20 of 37 in total

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  1. Tan SK, Yeong CH, Ng KH, Abdul Aziz YF, Sun Z
    PLoS One, 2016;11(8):e0161543.
    PMID: 27552224 DOI: 10.1371/journal.pone.0161543
    OBJECTIVES: This study aimed to measure the absorbed doses in selected organs for prospectively ECG-triggered coronary computed tomography angiography (CCTA) using five different generations CT scanners in a female adult anthropomorphic phantom and to estimate the effective dose (HE).

    MATERIALS AND METHODS: Prospectively ECG-triggered CCTA was performed using five commercially available CT scanners: 64-detector-row single source CT (SSCT), 2 × 32-detector-row-dual source CT (DSCT), 2 × 64-detector-row DSCT and 320-detector-row SSCT scanners. Absorbed doses were measured in 34 organs using pre-calibrated optically stimulated luminescence dosimeters (OSLDs) placed inside a standard female adult anthropomorphic phantom. HE was calculated from the measured organ doses and compared to the HE derived from the air kerma-length product (PKL) using the conversion coefficient of 0.014 mSv∙mGy-1∙cm-1 for the chest region.

    RESULTS: Both breasts and lungs received the highest radiation dose during CCTA examination. The highest HE was received from 2 × 32-detector-row DSCT scanner (6.06 ± 0.72 mSv), followed by 64-detector-row SSCT (5.60 ± 0.68 and 5.02 ± 0.73 mSv), 2 × 64-detector-row DSCT (1.88 ± 0.25 mSv) and 320-detector-row SSCT (1.34 ± 0.48 mSv) scanners. HE calculated from the measured organ doses were about 38 to 53% higher than the HE derived from the PKL-to-HE conversion factor.

    CONCLUSION: The radiation doses received from a prospectively ECG-triggered CCTA are relatively small and are depending on the scanner technology and imaging protocols. HE as low as 1.34 and 1.88 mSv can be achieved in prospectively ECG-triggered CCTA using 320-detector-row SSCT and 2 × 64-detector-row DSCT scanners.

    Matched MeSH terms: Organ Specificity/radiation effects
  2. Karami A, Golieskardi A, Ho YB, Larat V, Salamatinia B
    Sci Rep, 2017 07 14;7(1):5473.
    PMID: 28710445 DOI: 10.1038/s41598-017-05828-6
    There is a paucity of information about the occurrence of microplastics (MPs) in edible fish tissues. Here, we investigated the potential presence of MPs in the excised organs (viscera and gills) and eviscerated flesh (whole fish excluding the viscera and gills) of four commonly consumed dried fish species (n = 30 per species). The MP chemical composition was then determined using micro-Raman spectroscopy and elemental analysis with energy-dispersive X-ray spectroscopy (EDX). Out of 61 isolated particles, 59.0% were plastic polymers, 21.3% were pigment particles, 6.55% were non-plastic items (i.e. cellulose or actinolite), while 13.1% remained unidentified. The level of heavy metals on MPs or pigment particles were below the detection limit. Surprisingly, in two species, the eviscerated flesh contained higher MP loads than the excised organs, which highlights that evisceration does not necessarily eliminate the risk of MP intake by consumers. Future studies are encouraged to quantify anthropogenic particle loads in edible fish tissues.
    Matched MeSH terms: Organ Specificity*
  3. Sanusi MSM, Hassan WMSW, Hashim S, Ramli AT
    Appl Radiat Isot, 2021 Aug;174:109791.
    PMID: 34062400 DOI: 10.1016/j.apradiso.2021.109791
    Terrestrial radioactivity monitoring of 238U and 232Th series, and 40K in soil is an essential practice for radioactivity and radiation measurement of a place. In conventional practice, only basic data can be in-situ measured using a survey instrument, for example radioactivity concentration in soil and ambient dose equivalent rate. For other physical quantities, for example organ absorbed dose and organ equivalent dose, the measurement is impossible to be performed and can only be computed using Monte Carlo radiation transport simulations. In the past, most of the works only focused on calculating air-kerma-to-effective dose conversion factors. However, the information on organ dose conversion factors is scarcely documented and reported. This study was conducted to calculate organ absorbed and tissue-weighted equivalent dose conversion factors as a result of exposure from terrestrial gamma radiation. Series of organ dose conversion factors is produced based on computations from Monte Carlo MCNP5 simulations using modelled gamma irradiation geometry and established adult MIRD phantom. The study found out that most of the radiation exposed organs absorb energy at comparable rates, except for dense and superficial tissues i.e., skeleton and skin, which indicated slightly higher values. The good agreement between this work and previous studies demonstrated that our gamma irradiation geometry and modelling of gamma radiation sources are adequate. Therefore, the proposed organ dose conversion factors from this study are reasonably acceptable for dose estimation in environmental radioactivity monitoring practices.
    Matched MeSH terms: Organ Specificity*
  4. Mohammad MK, Mohamed MI, Zakaria AM, Abdul Razak HR, Saad WM
    Biomed Res Int, 2014;2014:512834.
    PMID: 24877107 DOI: 10.1155/2014/512834
    Watermelon is a natural product that contains high level of antioxidants and may prevent oxidative damage in tissues due to free radical generation following an exposure to ionizing radiation. The present study aimed to investigate the radioprotective effects of watermelon (Citrullus lanatus (Thunb.) Matsum. and Nakai) juice against oxidative damage induced by low dose X-ray exposure in mice. Twelve adult male ICR mice were randomly divided into two groups consisting of radiation (Rx) and supplementation (Tx) groups. Rx received filtered tap water, while Tx was supplemented with 50% (v/v) watermelon juice for 28 days ad libitum prior to total body irradiation by 100 μGy X-ray on day 29. Brain, lung, and liver tissues were assessed for the levels of malondialdehyde (MDA), apurinic/apyrimidinic (AP) sites, glutathione (GSH), and superoxide dismutase (SOD) inhibition activities. Results showed significant reduction of MDA levels and AP sites formation of Tx compared to Rx (P < 0.05). Mice supplemented with 50% watermelon juice restore the intracellular antioxidant activities by significantly increased SOD inhibition activities and GSH levels compared to Rx. These findings may postulate that supplementation of 50% watermelon (Citrullus lanatus (Thunb.) Matsum. and Nakai) juice could modulate oxidative damage induced by low dose X-ray exposure.
    Matched MeSH terms: Organ Specificity/drug effects; Organ Specificity/radiation effects
  5. Zakaria Z, Abdul Rahim R, Mansor MS, Yaacob S, Ayub NM, Muji SZ, et al.
    Sensors (Basel), 2012;12(6):7126-56.
    PMID: 22969341 DOI: 10.3390/s120607126
    Magnetic Induction Tomography (MIT), which is also known as Electromagnetic Tomography (EMT) or Mutual Inductance Tomography, is among the imaging modalities of interest to many researchers around the world. This noninvasive modality applies an electromagnetic field and is sensitive to all three passive electromagnetic properties of a material that are conductivity, permittivity and permeability. MIT is categorized under the passive imaging family with an electrodeless technique through the use of excitation coils to induce an electromagnetic field in the material, which is then measured at the receiving side by sensors. The aim of this review is to discuss the challenges of the MIT technique and summarize the recent advancements in the transmitters and sensors, with a focus on applications in biological tissue imaging. It is hoped that this review will provide some valuable information on the MIT for those who have interest in this modality. The need of this knowledge may speed up the process of adopted of MIT as a medical imaging technology.
    Matched MeSH terms: Organ Specificity*
  6. Jong WL, Wong JH, Ung NM, Ng KH, Ho GF, Cutajar DL, et al.
    J Appl Clin Med Phys, 2014 Sep 08;15(5):4869.
    PMID: 25207573 DOI: 10.1120/jacmp.v15i5.4869
    In vivo dosimetry is important during radiotherapy to ensure the accuracy of the dose delivered to the treatment volume. A dosimeter should be characterized based on its application before it is used for in vivo dosimetry. In this study, we characterize a new MOSFET-based detector, the MOSkin detector, on surface for in vivo skin dosimetry. The advantages of the MOSkin detector are its water equivalent depth of measurement of 0.07 mm, small physical size with submicron dosimetric volume, and the ability to provide real-time readout. A MOSkin detector was calibrated and the reproducibility, linearity, and response over a large dose range to different threshold voltages were determined. Surface dose on solid water phantom was measured using MOSkin detector and compared with Markus ionization chamber and GAFCHROMIC EBT2 film measurements. Dependence in the response of the MOSkin detector on the surface of solid water phantom was also tested for different (i) source to surface distances (SSDs); (ii) field sizes; (iii) surface dose; (iv) radiation incident angles; and (v) wedges. The MOSkin detector showed excellent reproducibility and linearity for dose range of 50 cGy to 300 cGy. The MOSkin detector showed reliable response to different SSDs, field sizes, surface, radiation incident angles, and wedges. The MOSkin detector is suitable for in vivo skin dosimetry.
    Matched MeSH terms: Organ Specificity/physiology*
  7. Wan Safwani WK, Makpol S, Sathapan S, Chua KH
    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: Organ Specificity/drug effects; Organ Specificity/genetics
  8. Borzák R, Borkhanuddin MH, Cech G, Molnár K, Hallett SL, Székely C
    Int J Parasitol Parasites Wildl, 2021 Aug;15:112-119.
    PMID: 33996443 DOI: 10.1016/j.ijppaw.2021.04.004
    Thelohanellus nikolskii, Achmerov, 1955 is a well-known myxozoan parasite of the common carp (Cyprinus carpio L.). Infection regularly manifests in numerous macroscopic cysts on the fins of two to three month-old pond-cultured carp fingerlings in July and August. However, a Thelohanellus infection is also common on the scales of two to three year-old common carp in ponds and natural waters in May and June. Based on myxospore morphology and tissue specificity, infection at both sites seems to be caused by the same species, namely T. nikolskii. This presumption was tested with molecular biological methods: SSU rDNA sequences of myxospores from fins of fingerlings and scales of older common carp were analysed and compared with each other and with related species available in GenBank. Sequence data revealed that the spores from the fins and scales represent the same species, T. nikolskii. Our study revealed a dichotomy in both infection site and time in T. nikolskii-infections: the fins of young carp are infected in Summer and Autumn, whereas the scales of older carp are infected in Spring. Myxosporean development of the species is well studied, little is known, however about the actinosporean stage of T. nikolskii. A previous experimental study suggests that aurantiactinomyxon actinospores of this species develop in Tubifex tubifex, Müller, 1774. The description included spore morphology but no genetic sequence data (Székely et al., 1998). We examined >9000 oligochaetes from Lake Balaton and Kis-Balaton Water Reservoire searching for the intraoligochaete developmental stage of myxozoans. Five oligochaete species were examined, Isochaetides michaelseni Lastochin, 1936, Branchiura sowerbyi Beddard, 1892, Nais sp., Müller, 1774, Dero sp. Müller, 1774 and Aelosoma sp. Ehrenberg, 1828. Morphometrics and SSU rDNA sequences were obtained for the released actinospores. Among them, from a single Nais sp., the sequence of an aurantiactinomyxon isolate corresponded to the myxospore sequences of T. nikolskii.
    Matched MeSH terms: Organ Specificity
  9. Low JZB, Khang TF, Tammi MT
    BMC Bioinformatics, 2017 12 28;18(Suppl 16):575.
    PMID: 29297307 DOI: 10.1186/s12859-017-1974-4
    BACKGROUND: In current statistical methods for calling differentially expressed genes in RNA-Seq experiments, the assumption is that an adjusted observed gene count represents an unknown true gene count. This adjustment usually consists of a normalization step to account for heterogeneous sample library sizes, and then the resulting normalized gene counts are used as input for parametric or non-parametric differential gene expression tests. A distribution of true gene counts, each with a different probability, can result in the same observed gene count. Importantly, sequencing coverage information is currently not explicitly incorporated into any of the statistical models used for RNA-Seq analysis.

    RESULTS: We developed a fast Bayesian method which uses the sequencing coverage information determined from the concentration of an RNA sample to estimate the posterior distribution of a true gene count. Our method has better or comparable performance compared to NOISeq and GFOLD, according to the results from simulations and experiments with real unreplicated data. We incorporated a previously unused sequencing coverage parameter into a procedure for differential gene expression analysis with RNA-Seq data.

    CONCLUSIONS: Our results suggest that our method can be used to overcome analytical bottlenecks in experiments with limited number of replicates and low sequencing coverage. The method is implemented in CORNAS (Coverage-dependent RNA-Seq), and is available at https://github.com/joel-lzb/CORNAS .

    Matched MeSH terms: Organ Specificity/genetics
  10. Pang SL, Ong SS, Lee HH, Zamri Z, Kandasamy KI, Choong CY, et al.
    Genet. Mol. Res., 2014;13(3):7217-38.
    PMID: 25222227 DOI: 10.4238/2014.September.5.7
    This study was directed at the understanding of the function of CCoAOMT isolated from Acacia auriculiformis x Acacia mangium. Full length cDNA of the Acacia hybrid CCoAOMT (AhCCoAOMT) was 1024-bp long, containing 750-bp coding regions, with one major open reading frame of 249 amino acids. On the other hand, full length genomic sequence of the CCoAOMT (AhgflCCoAOMT) was 2548 bp long, containing three introns and four exons with a 5' untranslated region (5'UTR) of 391 bp in length. The 5'UTR of the characterized CCoAOMT gene contains various regulatory elements. Southern analysis revealed that the Acacia hybrid has more than three copies of the CCoAOMT gene. Real-time PCR showed that this gene was expressed in root, inner bark, leaf, flower and seed pod of the Acacia hybrid. Downregulation of the homologous CCoAOMT gene in tobacco by antisense (AS) and intron-containing hairpin (IHP) constructs containing partial AhCCoAOMT led to reduction in lignin content. Expression of the CCoAOMT in AS line (pART-HAS78-03) and IHP line (pART-HIHP78-06) was reduced respectively by 37 and 75% compared to the control, resulting in a decrease in the estimated lignin content by 24 and 56%, respectively. AhCCoAOMT was found to have altered not only S and G units but also total lignin content, which is of economic value to the pulp industry. Subsequent polymorphism analysis of this gene across eight different genetic backgrounds each of A. mangium and A. auriculiformis revealed 47 single nucleotide polymorphisms (SNPs) in A. auriculiformis CCoAOMT and 30 SNPs in A. mangium CCoAOMT.
    Matched MeSH terms: Organ Specificity/genetics
  11. Ng WL, Marinov GK, Liau ES, Lam YL, Lim YY, Ea CK
    RNA Biol, 2016 09;13(9):861-71.
    PMID: 27362560 DOI: 10.1080/15476286.2016.1207036
    Circular RNAs (circRNAs) constitute a large class of RNA species formed by the back-splicing of co-linear exons, often within protein-coding transcripts. Despite much progress in the field, it remains elusive whether the majority of circRNAs are merely aberrant splicing by-products with unknown functions, or their production is spatially and temporally regulated to carry out specific biological functions. To date, the majority of circRNAs have been cataloged in resting cells. Here, we identify an LPS-inducible circRNA: mcircRasGEF1B, which is predominantly localized in cytoplasm, shows cell-type specific expression, and has a human homolog with similar properties, hcircRasGEF1B. We show that knockdown of the expression of mcircRasGEF1B reduces LPS-induced ICAM-1 expression. Additionally, we demonstrate that mcircRasGEF1B regulates the stability of mature ICAM-1 mRNAs. These findings expand the inventory of functionally characterized circRNAs with a novel RNA species that may play a critical role in fine-tuning immune responses and protecting cells against microbial infection.
    Matched MeSH terms: Organ Specificity/genetics
  12. Kar SP, Beesley J, Amin Al Olama A, Michailidou K, Tyrer J, Kote-Jarai Z, et al.
    Cancer Discov, 2016 Sep;6(9):1052-67.
    PMID: 27432226 DOI: 10.1158/2159-8290.CD-15-1227
    Breast, ovarian, and prostate cancers are hormone-related and may have a shared genetic basis, but this has not been investigated systematically by genome-wide association (GWA) studies. Meta-analyses combining the largest GWA meta-analysis data sets for these cancers totaling 112,349 cases and 116,421 controls of European ancestry, all together and in pairs, identified at P < 10(-8) seven new cross-cancer loci: three associated with susceptibility to all three cancers (rs17041869/2q13/BCL2L11; rs7937840/11q12/INCENP; rs1469713/19p13/GATAD2A), two breast and ovarian cancer risk loci (rs200182588/9q31/SMC2; rs8037137/15q26/RCCD1), and two breast and prostate cancer risk loci (rs5013329/1p34/NSUN4; rs9375701/6q23/L3MBTL3). Index variants in five additional regions previously associated with only one cancer also showed clear association with a second cancer type. Cell-type-specific expression quantitative trait locus and enhancer-gene interaction annotations suggested target genes with potential cross-cancer roles at the new loci. Pathway analysis revealed significant enrichment of death receptor signaling genes near loci with P < 10(-5) in the three-cancer meta-analysis.

    SIGNIFICANCE: We demonstrate that combining large-scale GWA meta-analysis findings across cancer types can identify completely new risk loci common to breast, ovarian, and prostate cancers. We show that the identification of such cross-cancer risk loci has the potential to shed new light on the shared biology underlying these hormone-related cancers. Cancer Discov; 6(9); 1052-67. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 932.

    Matched MeSH terms: Organ Specificity/genetics
  13. Ying CK, Kandaiya S
    J Radiol Prot, 2010 Sep;30(3):585-96.
    PMID: 20826892 DOI: 10.1088/0952-4746/30/3/012
    Interventional cardiology (IC) procedures are known to give high radiation doses to patients and cardiologists as they involve long fluoroscopy times and several cine runs. Patients' dose measurements were carried out at the cardiology department in a local hospital in Penang, Malaysia, using Gafchromic XR-RV2 films. The dosimetric properties of the Gafchromic film were first characterised. The film was energy and dose rate independent but dose dependent for the clinically used values. The film had reproducibility within ± 3% when irradiated on three different days and hence the same XR-RV2 dose-response calibration curve can be used to obtain patient entrance skin dose on different days. The increase in the response of the film post-irradiation was less than 4% over a period of 35 days. For patient dose measurements, the films were placed on the table underneath the patient for an under-couch tube position. This study included a total of 44 patients. Values of 35-2442 mGy for peak skin dose (PSD) and 10.9-344.4 Gy cm(2) for dose-area product (DAP) were obtained. DAP was found to be a poor indicator of PSD for PTCA procedures but there was a better correlation (R(2) = 0.7344) for CA + PTCA procedures. The highest PSD value in this study exceeded the threshold dose value of 2 Gy for early transient skin injury recommended by the Food and Drug Administration.
    Matched MeSH terms: Organ Specificity
  14. Ong LC, Chung FF, Tan YF, Leong CO
    Arch Toxicol, 2016 Jan;90(1):103-18.
    PMID: 25273022 DOI: 10.1007/s00204-014-1376-6
    Carbon nanotubes (CNTs) are an important class of nanomaterials, which have numerous novel properties that make them useful in technology and industry. Generally, there are two types of CNTs: single-walled nanotubes (SWNTs) and multi-walled nanotubes. SWNTs, in particular, possess unique electrical, mechanical, and thermal properties, allowing for a wide range of applications in various fields, including the electronic, computer, aerospace, and biomedical industries. However, the use of SWNTs has come under scrutiny, not only due to their peculiar nanotoxicological profile, but also due to the forecasted increase in SWNT production in the near future. As such, the risk of human exposure is likely to be increased substantially. Yet, our understanding of the toxicological risk of SWNTs in human biology remains limited. This review seeks to examine representative data on the nanotoxicity of SWNTs by first considering how SWNTs are absorbed, distributed, accumulated and excreted in a biological system, and how SWNTs induce organ-specific toxicity in the body. The contradictory findings of numerous studies with regards to the potential hazards of SWNT exposure are discussed in this review. The possible mechanisms and molecular pathways associated with SWNT nanotoxicity in target organs and specific cell types are presented. We hope that this review will stimulate further research into the fundamental aspects of CNTs, especially the biological interactions which arise due to the unique intrinsic characteristics of CNTs.
    Matched MeSH terms: Organ Specificity
  15. Lim CH, Soga T, Levavi-Sivan B, Parhar IS
    Sci Rep, 2020 05 06;10(1):7666.
    PMID: 32376994 DOI: 10.1038/s41598-020-64639-4
    Spexin (SPX), a neuropeptide evolutionarily conserved from fish to mammals, is widely distributed in the brain and peripheral tissues and associated with various physiological functions. Recently SPX has been suggested to be involved in neurological mechanism of stress. The current study investigates the involvement of SPX in chronic social defeat stress, using male teleost, the Nile tilapia (Oreochromis niloticus) as an animal model due to its distinct social hierarchy of dominant and subordinate relationship. The tilapia genome has SPX1a and SPX1b but has no SPX2. In the Nile tilapia, we localized SPX1a and SPX1b in the brain using in-situ hybridization. Next, using qPCR we examined gene expression of SPX1a and SPX1b in chronically stress (socially defeated) fish. SPX1a expressing cells were localized in the semicircular torus of the midbrain region and SPX1b expressing cells in the telencephalon. Chronically stress fish showed elevated plasma cortisol levels; with an upregulation of SPX1a and SPX1b gene expression in the brain compared to non-stress (control) fish. Since social defeat is a source of stress, the upregulated SPX mRNA levels during social defeat suggests SPX as a potentially inhibitory neuropeptide capable of causing detrimental changes in behaviour and physiology.
    Matched MeSH terms: Organ Specificity
  16. Everest-Dass AV, Briggs MT, Kaur G, Oehler MK, Hoffmann P, Packer NH
    Mol Cell Proteomics, 2016 09;15(9):3003-16.
    PMID: 27412689 DOI: 10.1074/mcp.M116.059816
    Ovarian cancer is a fatal gynaecological malignancy in adult women with a five-year overall survival rate of only 30%. Glycomic and glycoproteomic profiling studies have reported extensive protein glycosylation pattern alterations in ovarian cancer. Therefore, spatio-temporal investigation of these glycosylation changes may unearth tissue-specific changes that occur in the development and progression of ovarian cancer. A novel method for investigating tissue-specific N-linked glycans is using matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) on formalin-fixed paraffin-embedded (FFPE) tissue sections that can spatially profile N-glycan compositions released from proteins in tissue-specific regions. In this study, tissue regions of interest (e.g. tumor, stroma, adipose tissue and necrotic areas) were isolated from FFPE tissue sections of advanced serous ovarian cancers (n = 3). PGC-LC-ESI-MS/MS and MALDI-MSI were used as complementary techniques to firstly generate structural information on the tissue-specific glycans in order to then obtain high resolution images of the glycan structure distribution in ovarian cancer tissue. The N-linked glycan repertoires carried by the proteins in these tissue regions were structurally characterized for the first time in FFPE ovarian cancer tissue regions, using enzymatic peptide-N-glycosidase F (PNGase F) release of N-glycans. The released glycans were analyzed by porous graphitized carbon liquid chromatography (PGC-LC) and collision induced electrospray negative mode MS fragmentation analysis. The N-glycan profiles identified by this analysis were then used to determine the location and distribution of each N-glycan on FFPE ovarian cancer sections that were treated with PNGase F using high resolution MALDI-MSI. A tissue-specific distribution of N-glycan structures identified particular regions of the ovarian cancer sections. For example, high mannose glycans were predominantly expressed in the tumor tissue region whereas complex/hybrid N-glycans were significantly abundant in the intervening stroma. Therefore, tumor and non-tumor tissue regions were clearly demarcated solely on their N-glycan structure distributions.
    Matched MeSH terms: Organ Specificity
  17. Chiew MY, Boo NY, Voon K, Cheong SK, Leong PP
    Leuk Lymphoma, 2017 01;58(1):162-170.
    PMID: 27185517
    Acute monocytic leukemia (AML-M5), a subtype of acute myeloid leukemia (AML), affects mostly young children and has poor prognosis. The mechanisms of treatment failure of AML-M5 are still unclear. In this study, we generated iPSC from THP-1 cells from a patient with AML-M5, using retroviruses encoding the pluripotency-associated genes (OCT3/4, SOX2, KLF4 and c-MYC). These AML-M5-derived iPSC showed features similar with those of human embryonic stem cells in terms of the morphology, gene expression, protein/antigen expression and differentiation capability. Parental-specific markers were down-regulated in these AML-M5-derived iPSCs. Expression of MLL-AF9 fusion gene (previously identified to be associated with pathogenesis of AML-M5) was observed in all iPSC clones as well as parental cells. We conclude that AML-M5-specific iPSC clones have been successfully developed. This disease model may provide a novel approach for future study of pathogenesis and therapeutic intervention of AML-M5.
    Matched MeSH terms: Organ Specificity/genetics
  18. Samuel MS, Rath N, Masre SF, Boyle ST, Greenhalgh DA, Kochetkova M, et al.
    Genesis, 2016 Dec;54(12):636-646.
    PMID: 27775859 DOI: 10.1002/dvg.22988
    The serine/threonine kinases ROCK1 and ROCK2 are central mediators of actomyosin contractile force generation that act downstream of the RhoA small GTP-binding protein. As a result, they have key roles in regulating cell morphology and proliferation, and have been implicated in numerous pathological conditions and diseases including hypertension and cancer. Here we describe the generation of a gene-targeted mouse line that enables CRE-inducible expression of a conditionally-active fusion between the ROCK2 kinase domain and the hormone-binding domain of a mutated estrogen receptor (ROCK2:ER). This two-stage system of regulation allows for tissue-selective expression of the ROCK2:ER fusion protein, which then requires administration of estrogen analogues such as tamoxifen or 4-hydroxytamoxifen to elicit kinase activity. This conditional gain-of-function system was validated in multiple tissues by crossing with mice expressing CRE recombinase under the transcriptional control of cytokeratin14 (K14), murine mammary tumor virus (MMTV) or cytochrome P450 Cyp1A1 (Ah) promoters, driving appropriate expression in the epidermis, mammary or intestinal epithelia respectively. Given the interest in ROCK signaling in normal physiology and disease, this mouse line will facilitate research into the consequences of ROCK activation that could be used to complement conditional knockout models. Birth Defects Research (Part A) 106:636-646, 2016. © 2016 Wiley Periodicals, Inc.
    Matched MeSH terms: Organ Specificity/genetics
  19. Lee HC, Hamzah H, Leong MP, Md Yusof H, Habib O, Zainal Abidin S, et al.
    Sci Rep, 2021 Feb 15;11(1):3847.
    PMID: 33589712 DOI: 10.1038/s41598-021-83222-z
    Ruxolitinib is the first janus kinase 1 (JAK1) and JAK2 inhibitor that was approved by the United States Food and Drug Administration (FDA) agency for the treatment of myeloproliferative neoplasms. The drug targets the JAK/STAT signalling pathway, which is critical in regulating the gliogenesis process during nervous system development. In the study, we assessed the effect of non-maternal toxic dosages of ruxolitinib (0-30 mg/kg/day between E7.5-E20.5) on the brain of the developing mouse embryos. While the pregnant mice did not show any apparent adverse effects, the Gfap protein marker for glial cells and S100β mRNA marker for astrocytes were reduced in the postnatal day (P) 1.5 pups' brains. Gfap expression and Gfap+ cells were also suppressed in the differentiating neurospheres culture treated with ruxolitinib. Compared to the control group, adult mice treated with ruxolitinib prenatally showed no changes in motor coordination, locomotor function, and recognition memory. However, increased explorative behaviour within an open field and improved spatial learning and long-term memory retention were observed in the treated group. We demonstrated transplacental effects of ruxolitinib on astrogenesis, suggesting the potential use of ruxolitinib to revert pathological conditions caused by gliogenic-shift in early brain development such as Down and Noonan syndromes.
    Matched MeSH terms: Organ Specificity/drug effects
  20. Lee JH, Pooley NJ, Mohd-Adnan A, Martin SA
    PLoS One, 2014;9(7):e103729.
    PMID: 25078784 DOI: 10.1371/journal.pone.0103729
    Ferritin is a highly-conserved iron-storage protein that has also been identified as an acute phase protein within the innate immune system. The iron-storage function is mediated through complementary roles played by heavy (H)-chain subunit as well as the light (L) in mammals or middle (M)-chain in teleosts, respectively. In this study, we report the identification of five ferritin subunits (H1, H2, M1, M2, M3) in the Atlantic salmon that were supported by the presence of iron-regulatory regions, gene structure, conserved domains and phylogenetic analysis. Tissue distribution analysis across eight different tissues showed that each of these isoforms is differentially expressed. We also examined the expression of the ferritin isoforms in the liver and kidney of juvenile Atlantic salmon that was challenged with Aeromonas salmonicida as well as in muscle cell culture stimulated with interleukin-1β. We found that each isoform displayed unique expression profiles, and in certain conditions the expressions between the isoforms were completely diametrical to each other. Our study is the first report of multiple ferritin isoforms from both the H- and M-chains in a vertebrate species, as well as ferritin isoforms that showed decreased expression in response to infection. Taken together, the results of our study suggest the possibility of functional differences between the H- and M-chain isoforms in terms of tissue localisation, transcriptional response to bacterial exposure and stimulation by specific immune factors.
    Matched MeSH terms: Organ Specificity
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