Browse publications by year: 2016

  1. Abdul Hamid Z, Mohd Zulkifly MF, Hamid A, Lubis SH, Mohammad N, Ishak I, et al.
    Genes Environ, 2016;38:7.
    PMID: 27350827 DOI: 10.1186/s41021-016-0032-1
    Pesticide exposure possesses risk of genotoxicity to humans, particularly farmers. Despite accumulating evidences linking genotoxicity to pesticide exposure, epidemiological studies to address pesticide toxicity in occupationally exposed farmers in Malaysia remain underreported. Thus, this study was aimed to determine the presence of nuclear abnormalities through the assessment of micronucleus (MN) and binucleus (BNu) frequencies in exfoliated buccal epithelial cells from farmers who were exposed to pesticides. A cross-sectional study of farmers among different agricultural activities farmers in Bachok and Pasir Puteh, Kelantan, North East of Peninsular Malaysia was done to evaluate the presence of nuclear abnormalities and its correlation with their health status and farming activities.
  2. Ab Mutalib NS, Othman SN, Mohamad Yusof A, Abdullah Suhaimi SN, Muhammad R, Jamal R
    PeerJ, 2016;4:e2119.
    PMID: 27350898 DOI: 10.7717/peerj.2119
    Background. Papillary thyroid carcinoma (PTC) is the commonest thyroid malignancy originating from the follicle cells in the thyroid. Despite a good overall prognosis, certain high-risk cases as in those with lymph node metastasis (LNM) have progressive disease and poorer prognosis. MicroRNAs are a class of non-protein-coding, 19-24 nucleotides single-stranded RNAs which regulate gene expression and these molecules have been shown to play a role in LNM. The integrated analysis of miRNAs and gene expression profiles together with transcription factors (TFs) has been shown to improve the identification of functional miRNA-target gene-TF relationships, providing a more complete view of molecular events underlying metastasis process. Objectives. We reanalyzed The Cancer Genome Atlas (TCGA) datasets on PTC to identify differentially expressed miRNAs/genes in PTC patients with LNM-positive (LNM-P) versus lymph node negative (LNN) PTC patients and to investigate the miRNA-gene-TF regulatory circuit that regulate LNM in PTC. Results. PTC patients with LNM (PTC LNM-P) have a significantly shorter disease-free survival rate compared to PTC patients without LNM (PTC LNN) (Log-rank Mantel Cox test, p = 0.0049). We identified 181 significantly differentially expressed miRNAs in PTC LNM-P versus PTC LNN; 110 were upregulated and 71 were downregulated. The five topmost deregulated miRNAs were hsa-miR-146b, hsa-miR-375, hsa-miR-31, hsa-miR-7-2 and hsa-miR-204. In addition, 395 miRNAs were differentially expressed between PTC LNM-P and normal thyroid while 400 miRNAs were differentially expressed between PTC LNN and normal thyroid. We found four significant enrichment pathways potentially involved in metastasis to the lymph nodes, namely oxidative phosphorylation (OxPhos), cell adhesion molecules (CAMs), leukocyte transendothelial migration and cytokine-cytokine receptor interaction. OxPhos was the most significantly perturbed pathway (p = 4.70E-06) involving downregulation of 90 OxPhos-related genes. Significant interaction of hsa-miR-301b with HLF, HIF and REL/NFkB transcription factors were identified exclusively in PTC LNM-P versus PTC LNN. Conclusion. We found evidence of five miRNAs differentially expressed in PTC LNM-P. Alteration in OxPhos pathway could be the central event in metastasis to the lymph node in PTC. We postulate that hsa-miR-301b might be involved in regulating LNM in PTC via interactions with HLF, HIF and REL/NFkB. To the best of our knowledge, the roles of these TFs have been studied in PTC but the precise role of this miRNA with these TFs in LNM in PTC has not been investigated.
    MeSH terms: Humans; Lymphatic Metastasis; Nucleotides; Oxidative Phosphorylation; Thyroid Neoplasms; Transcription Factors; Down-Regulation; Up-Regulation; Disease-Free Survival; MicroRNAs; Transendothelial and Transepithelial Migration; Transcriptome
  3. Jahidin AH, Stewart TA, Thompson EW, Roberts-Thomson SJ, Monteith GR
    Biochem Biophys Res Commun, 2016 Sep 02;477(4):731-736.
    PMID: 27353380 DOI: 10.1016/j.bbrc.2016.06.127
    Two-pore channel proteins, TPC1 and TPC2, are calcium permeable ion channels found localized to the membranes of endolysosomal calcium stores. There is increasing interest in the role of TPC-mediated intracellular signaling in various pathologies; however their role in breast cancer has not been extensively evaluated. TPC1 and TPC2 mRNA was present in all non-tumorigenic and tumorigenic breast cell lines assessed. Silencing of TPC2 but not TPC1 attenuated epidermal growth factor-induced vimentin expression in MDA-MB-468 breast cancer cells. This effect was not due to a general inhibition of epithelial to mesenchymal transition (EMT) as TPC2 silencing had no effect on epidermal growth factor (EGF)-induced changes on E-cadherin expression. TPC1 and TPC2 were also shown to differentially regulate cyclopiazonic acid (CPA)-mediated changes in cytosolic free Ca(2+). These findings indicate potential differential regulation of signaling processes by TPC1 and TPC2 in breast cancer cells.
    MeSH terms: Breast Neoplasms/metabolism*; Calcium/metabolism; Female; Humans; Receptor, Epidermal Growth Factor/metabolism*; Vimentin/metabolism*; Calcium Channels/genetics; Calcium Channels/metabolism*; Ion Channel Gating; Gene Expression Regulation, Neoplastic; Calcium Signaling*; Gene Silencing; Cell Line, Tumor
  4. Lo TS, Huang YH, Dass AK, Karim N, Uy-Patrimonio MC
    J Obstet Gynaecol Res, 2016 Oct;42(10):1361-1368.
    PMID: 27354199 DOI: 10.1111/jog.13066
    AIM: To identify the favorable factors in rectovaginal fistula (RVF) management.

    METHODS: After Institutional Review Board approval (99-0793B), we retrospectively studied all patients diagnosed, treated and followed up with RVF at Chang Gung Memorial Hospital, Taiwan between January 1990 and December 2009. All female patients with International Classification of Diseases RVF were included. We reviewed demographic data, socioeconomic status, clinical presentation, comorbidities, method of treatment, duration of hospitalization and clinical outcome at 12 months postoperatively.

    RESULTS: A total of 397 patients were included in the study. Fifty-six patients (14.1%) had conservative treatment and 341 patients (85.9%) underwent surgical intervention. A total of 125 patients underwent simple repair while 216 patients underwent reconstruction. Three hundred and forty-four patients (86.7%) had improved outcome at 12-month follow up. Age (P = 0.003), education level (P = 0.033), ability to pay insurance (P < 0.001), and choice of treatment (P < 0.0001) were identified as significant favorable factors. An etiological factor associated with favorable outcome was RVF from obstetric complication, while that resulting from malignancy had a less favorable outcome.

    CONCLUSIONS: Age, education level and ability to pay insurance significantly affect 12-month outcome of RVF. Surgery is the preferred option, while medical treatment should be used only for small rectovaginal fistulas or for patients not suitable for surgery and anesthesia. More support and assistance should be offered to those patients with unfavorable factors, such as old age, low education level and inability to afford insurance. All RVF secondary to obstetrical injury had a 100% favorable outcome compared with those secondary to surgery or malignancy. Women with suspected RVF should receive prompt and extensive evaluation to ensure immediate effective management and prevention of further serious complications.

    MeSH terms: Female; Humans; Middle Aged; Rectovaginal Fistula/epidemiology*; Rectovaginal Fistula/surgery*; Retrospective Studies; Taiwan; Treatment Outcome
  5. Arzmi MH, Alnuaimi AD, Dashper S, Cirillo N, Reynolds EC, McCullough M
    Med Mycol, 2016 Nov 01;54(8):856-64.
    PMID: 27354487 DOI: 10.1093/mmy/myw042
    Oral biofilms comprise of extracellular polysaccharides and polymicrobial microorganisms. The objective of this study was to determine the effect of polymicrobial interactions of Candida albicans, Actinomyces naeslundii, and Streptococcus mutans on biofilm formation with the hypotheses that biofilm biomass and metabolic activity are both C. albicans strain and growth medium dependent. To study monospecific biofilms, C. albicans, A. naeslundii, and S. mutans were inoculated into artificial saliva medium (ASM) and RPMI-1640 in separate vials, whereas to study polymicrobial biofilm formation, the inoculum containing microorganisms was prepared in the same vial prior inoculation into a 96-well plate followed by 72 hours incubation. Finally, biofilm biomass and metabolic activity were measured using crystal violet and XTT assays, respectively. Our results showed variability of monospecies and polymicrobial biofilm biomass between C. albicans strains and growth medium. Based on cut-offs, out of 32, seven RPMI-grown biofilms had high biofilm biomass (HBB), whereas, in ASM-grown biofilms, 14 out of 32 were HBB. Of the 32 biofilms grown in RPMI-1640, 21 were high metabolic activity (HMA), whereas in ASM, there was no biofilm had HMA. Significant differences were observed between ASM and RPMI-grown biofilms with respect to metabolic activity (P <01). In conclusion, biofilm biomass and metabolic activity were both C. albicans strain and growth medium dependent.
    MeSH terms: Actinomyces/growth & development; Actinomyces/metabolism; Actinomyces/physiology*; Candida albicans/growth & development; Candida albicans/metabolism; Candida albicans/physiology*; Culture Media/chemistry*; Formazans/analysis; Gentian Violet/analysis; Models, Biological; Saliva/microbiology; Staining and Labeling; Streptococcus mutans/growth & development; Streptococcus mutans/metabolism; Streptococcus mutans/physiology*; Biofilms/growth & development*; Microbial Interactions*
  6. Yuandani, Jantan I, Ilangkovan M, Husain K, Chan KM
    Drug Des Devel Ther, 2016;10:1935-45.
    PMID: 27354767 DOI: 10.2147/DDDT.S105651
    Standardized extract of Phyllanthus amarus has previously been shown to have a strong inhibitory effect on phagocytic activity of human neutrophils. The current study was carried out to evaluate the effects of constituents of the extract of P. amarus on nitric oxide (NO) production as well as lymphocyte proliferation and cytokine release from phagocytes. Three compounds, ethyl 8-hydroxy-8-methyl-tridecanoate, 7β,19α dihydroxy-urs-12-ene, and 1,7,8-trihydroxy-2-naphtaldehyde, together with seven known compounds were isolated from the whole plant of P. amarus. The isolated compounds and reference standards, ie, gallic acid, ellagic acid, corilagin, and geraniin, which were quantitatively analyzed in the extracts, were evaluated for their effects on immune cells. Among the compounds tested, the lignans, especially phyltetralin and phyllanthin, showed strong inhibition on lymphocyte proliferation with half maximal inhibitory concentration (IC50) values of 1.07 μM and 1.82 μM, respectively. Ethyl 8-hydroxy-8-methyl-tridecanoate and 1,7,8-trihydroxy-2-naphtaldehyde exhibited strong inhibition on nitric oxide production with IC50 values of 0.91 μM and 1.07 μM, respectively. Of all the compounds, corilagin was the strongest inhibitor of tumor necrosis factor-α release with an IC50 value of 7.39 μM, whereas geraniin depicted the strongest inhibitory activity on interleukin-1β release with an IC50 value of 16.41 μM. The compounds constituting the extract of P. amarus were able to inhibit the innate immune response of phagocytes at different steps.
    MeSH terms: Humans; Lymphocyte Activation; Lymphocytes/drug effects*; Lymphocytes/chemistry; Nitric Oxide/chemistry*; Phagocytes/drug effects*; Plant Extracts/pharmacology; Triterpenes/isolation & purification; Triterpenes/pharmacology*; Triterpenes/chemistry*; Lignans/isolation & purification; Lignans/pharmacology*; Lignans/chemistry*; Phyllanthus/chemistry*; Interleukin-1beta/antagonists & inhibitors*; Interleukin-1beta/chemistry
  7. Bhagat V, Haque M, Simbak NB, Jaalam K
    Adv Med Educ Pract, 2016;7:341-6.
    PMID: 27354836 DOI: 10.2147/AMEP.S108477
    Personality dimension negative emotionality is known to be associated with academic achievement. The present study focuses on the influence of negative emotionality (neuroticism) on the medical students' academic achievements. The main objective of this study was to ascertain the negative emotionality scores among the first year Malaysian medical students studying in Malaysia and India, further to find out the association between negative emotionality and their academic achievements. The current study sample includes 60 first year Malaysian medical students from Universiti Sultan Zainal Abidin, Malaysia, and USM-KLE IMP, Belgaum, India. They were selected by convenient sampling technique. The Medico-Psychological questionnaire was used to find out the negative emotionality scores among the students and these scores were compared with academic scores. The data were analyzed using SPSS- 20. Thus, the study result goes with the prediction that there is a significant correlation between academic achievement and negative emotionality. We concluded that negative emotionality has a negative impact on medical student's academic achievement regardless of the fact whether they study in their own country or overseas.
    MeSH terms: Eugenol; India; Inosine Monophosphate; Malaysia; Surveys and Questionnaires; Students, Medical; Zinc Oxide
  8. Salama M, Mohamed WM
    Appl Transl Genom, 2016 Jun;9:20-2.
    PMID: 27354936 DOI: 10.1016/j.atg.2016.03.001
    Asphyxial death has been a problem for forensic investigations due to the absence of a validated biomarker for the diagnosis of this event. Recently, research on brain affection by asphyxia raised hopes on the possible use of CNS markers for asphyxia. The cytoskeletal proteins seem to be attractive targets as they are vulnerable to hypoxia and can be affected in asphyxial deaths. Tau, an important cytoskeletal protein, showed affection in many neurodegenerative disorders and recently in some acute incidences like trauma and brain ischemia. In this report we show the affection of the normal pattern of tau and pathological aggregates of tau in the case of brain hypoxia. This may give new clues to asphyxial death investigations.
  9. Miswan MF, Al-Fayyadh MZ, Seow Hui T, Mohamed Ali MR, Ng WM
    Arthrosc Tech, 2016 Apr;5(2):e321-7.
    PMID: 27354953 DOI: 10.1016/j.eats.2016.01.003
    A patient with patellar instability frequently presents with anterior knee pain, patellar subluxation, or dislocation. Medial patellofemoral ligament (MPFL) has a key role for normal patella tracking and stability. Reconstruction of the MPFL using a hamstring graft is a commonly used procedure for the treatment of chronic lateral subluxation of patella. Anchor sutures and bony tunnels are used for the patellar attachment of the graft. This can be associated with complications such as patella fracture; besides, it does not produce an anatomical reconstruction for the native MPFL that can alter the direction of tension applied on the patella. To overcome these problems, a soft-tissue loop technique is used for MPFL reconstruction. During this procedure, a semitendinosus graft was passed through the prepatellar extensor retinaculum and secured with sutures. The free ends of the graft were then passed between the second and third layers of the medial patellofemoral retinaculum and fixed to a femoral tunnel on the medial femoral condyle with an interference screw. The desired amount of tension on the graft is achieved under direct vision of patella tracking arthroscopically. We found this method to be relatively safe and fast. It is more anatomical and can avoid the complications during the conventional bony procedures.
  10. Baharin MF, Dhaliwal JS, Sarachandran SV, Idris SZ, Yeoh SL
    J Med Case Rep, 2016;10(1):188.
    PMID: 27356510 DOI: 10.1186/s13256-016-0944-1
    Wiskott-Aldrich syndrome is a rare X-linked disorder characterized by microthrombocytopenia, eczema, and recurrent infections. It is caused by mutations of the WAS gene. Microthrombocytopenia has been regarded as the key criteria in diagnosing this rare condition. However, in this case report, we describe a case of Wiskott-Aldrich syndrome with normal platelet size.
  11. Stahl FW, Rehan MB, Foss HM, Borts RH
    Genetics, 2016 Jun 29.
    PMID: 27356614
    Previously published, and some unpublished, tetrad data from budding yeast (Saccharomyces cerevisiae) are analyzed for disparity in gene conversion, in which one allele is more often favored than the other ("conversion disparity"). One such disparity, characteristic of a bias in the frequencies of meiotic double-strand DNA breaks at the hotspot near the His4 locus, is found in diploids that undergo meiosis soon after their formation, but not in diploids that have been cloned and frozen. Altered meiotic DNA-breakability associated with altered metabolism-related chromatin states has been previously reported. However, the above observations imply that such differing parental chromatin states can persist through at least one chromosome replication, and probably more, in a common environment. This conclusion may have implications for interpreting changes in allele frequencies in populations.
  12. Jinap S, Hajeb P, Karim R, Norliana S, Yibadatihan S, Abdul-Kadir R
    Food Nutr Res, 2016;60:30463.
    PMID: 27356909 DOI: 10.3402/fnr.v60.30463
    Excessive dietary sodium intake causes several diseases, such as hypertension, cardiovascular and renal disease, etc. Hence, reducing sodium intake has been highly recommended. In this study the effect of monosodium glutamate (MSG), as an umami substance, on saltiness and sodium reduction was investigated.
  13. Iijima C, Wong CP, Nugroho AE, Sotozono Y, Someya S, Hirasawa Y, et al.
    J Nat Med, 2016 Oct;70(4):702-7.
    PMID: 27357963 DOI: 10.1007/s11418-016-1016-y
    The ceramicines, a series of limonoids from Chisocheton ceramicus (Meliaceae), were evaluated for anti-melanin deposition activity on α-melanocyte stimulating hormone (α-MSH) and 3-isobutyl-1-methylxanthine (IBMX)-treated B16-F10 melanoma cell, and several ceramicines were found to be active. The structure-activity relationship of ceramicines as anti-melanin deposition inhibitors was deduced. Furthermore, the mechanism of anti-melanin deposition activity of ceramicine B, a major constituent of C. ceramicus that showed potent anti-melanin deposition activity, was investigated. Tyrosinase enzymatic activity and tyrosinase mRNA expression were not affected by ceramicine B. The anti-melanin deposition activity of ceramicine B was shown to be related to the downregulation of tyrosinase protein expression. These results suggest that ceramicines have potential to be used as depigmentation agents.
    MeSH terms: Animals; Melanins/biosynthesis; Melanins/metabolism*; Melanoma, Experimental/metabolism*; Pigmentation/drug effects; Plant Extracts/pharmacology*; Structure-Activity Relationship; Monophenol Monooxygenase/metabolism*; Down-Regulation/drug effects; Meliaceae/chemistry*; Limonins/pharmacology*; Cell Line, Tumor; Mice
  14. Colwell RK, Gotelli NJ, Ashton LA, Beck J, Brehm G, Fayle TM, et al.
    Ecol Lett, 2016 09;19(9):1009-22.
    PMID: 27358193 DOI: 10.1111/ele.12640
    We introduce a novel framework for conceptualising, quantifying and unifying discordant patterns of species richness along geographical gradients. While not itself explicitly mechanistic, this approach offers a path towards understanding mechanisms. In this study, we focused on the diverse patterns of species richness on mountainsides. We conjectured that elevational range midpoints of species may be drawn towards a single midpoint attractor - a unimodal gradient of environmental favourability. The midpoint attractor interacts with geometric constraints imposed by sea level and the mountaintop to produce taxon-specific patterns of species richness. We developed a Bayesian simulation model to estimate the location and strength of the midpoint attractor from species occurrence data sampled along mountainsides. We also constructed midpoint predictor models to test whether environmental variables could directly account for the observed patterns of species range midpoints. We challenged these models with 16 elevational data sets, comprising 4500 species of insects, vertebrates and plants. The midpoint predictor models generally failed to predict the pattern of species midpoints. In contrast, the midpoint attractor model closely reproduced empirical spatial patterns of species richness and range midpoints. Gradients of environmental favourability, subject to geometric constraints, may parsimoniously account for elevational and other patterns of species richness.
    MeSH terms: Animals; Bayes Theorem; Insects/physiology; Models, Biological*; Vertebrates/physiology; Ecosystem*; Plant Physiological Phenomena; Biodiversity*
  15. Kremastinou J, Polymerou V, Lavranos D, Aranda Arrufat A, Harwood J, Martínez Lorenzo MJ, et al.
    J Clin Microbiol, 2016 09;54(9):2330-6.
    PMID: 27358468 DOI: 10.1128/JCM.02544-15
    Treponema pallidum infections can have severe complications if not diagnosed and treated at an early stage. Screening and diagnosis of syphilis require assays with high specificity and sensitivity. The Elecsys Syphilis assay is an automated treponemal immunoassay for the detection of antibodies against T. pallidum The performance of this assay was investigated previously in a multicenter study. The current study expands on that evaluation in a variety of diagnostic settings and patient populations, at seven independent laboratories. The samples included routine diagnostic samples, blood donation samples, samples from patients with confirmed HIV infections, samples from living organ or bone marrow donors, and banked samples, including samples previously confirmed as syphilis positive. This study also investigated the seroconversion sensitivity of the assay. With a total of 1,965 syphilis-negative routine diagnostic samples and 5,792 syphilis-negative samples collected from blood donations, the Elecsys Syphilis assay had specificity values of 99.85% and 99.86%, respectively. With 333 samples previously identified as syphilis positive, the sensitivity was 100% regardless of disease stage. The assay also showed 100% sensitivity and specificity with samples from 69 patients coinfected with HIV. The Elecsys Syphilis assay detected infection in the same bleed or earlier, compared with comparator assays, in a set of sequential samples from a patient with primary syphilis. In archived serial blood samples collected from 14 patients with direct diagnoses of primary syphilis, the Elecsys Syphilis assay detected T. pallidum antibodies for 3 patients for whom antibodies were not detected with the Architect Syphilis TP assay, indicating a trend for earlier detection of infection, which may have the potential to shorten the time between infection and reactive screening test results.
    MeSH terms: Antibodies, Bacterial/blood; Humans; Immunoassay/methods*; Mass Screening/methods*; Sensitivity and Specificity; Syphilis/diagnosis*; Treponema pallidum/isolation & purification*; Early Diagnosis; Automation, Laboratory/methods*
  16. Ali NM, Akhtar MN, Ky H, Lim KL, Abu N, Zareen S, et al.
    Drug Des Devel Ther, 2016;10:1897-907.
    PMID: 27358555 DOI: 10.2147/DDDT.S102164
    Known as naturally occurring biologically active compounds, flavokawain A and B are the leading chalcones that possess anticancer properties. Another flavokawain derivative, (E)-1-(2'-Hydroxy-4',6'-dimethoxyphenyl)-3-(4-methylthio)phenyl)prop-2-ene-1-one (FLS) was characterized with (1)H-nuclear magnetic resonance, electron-impact mas spectrometry, infrared spectroscopy, and ultraviolet ((1)H NMR, EI-MS, IR, and UV) spectroscopic techniques. FLS cytotoxic efficacy against human cancer cells (MCF-7, MDA-MB-231, and MCF-10A) resulted in the reduction of IC50 values in a time- and dose-dependent mode with high specificity on MCF-7 (IC50 of 36 μM at 48 hours) against normal breast cell MCF-10A (no IC50 detected up to 180 μM at 72 hours). Light, scanning electron, and fluorescent microscopic analysis of MCF-7 cells treated with 36 μM of FLS displayed cell shrinkage, apoptotic body, and DNA fragmentation. Additionally, induction of G2/M cell arrest within 24 hours and apoptosis at subsequent time points was discovered via flow cytometry analysis. The roles of PLK-1, Wee-1, and phosphorylation of CDC-2 in G2/M arrest and proapoptotic factors (Bax, caspase 9, and p53) in promotion of apoptosis of FLS against MCF-7 cells were discovered using fluorometric, quantitative real-time polymerase chain reaction, and Western blot analysis. Interestingly, the presence of SCH3 (thiomethyl group) on ring B structure contributed to the selective cytotoxicity against MCF-7 cells compared to other chalcones, flavokawain A and B. Overall, our data suggest potential therapeutic value for flavokawain derivative FLS to be further developed as a new anticancer drug.
  17. Chin KY, Kamaruddin AA, Low NY, Ima-Nirwana S
    Clin Interv Aging, 2016;11:767-73.
    PMID: 27358558 DOI: 10.2147/CIA.S108772
    Osteoporosis is a significant health problem in the developing countries and its prevalence data are important for the estimation of health care burden and policy making. This study aimed to determine the age-related changes in bone health and the prevalence of osteoporosis in males and females aged 50 years or above living in Kuala Lumpur, Malaysia.
    MeSH terms: Aged; Aged, 80 and over; Aging*; Anthropometry; Cross-Sectional Studies; Female; Health Status*; Humans; Malaysia; Male; Middle Aged; Ultrasonography; Absorptiometry, Photon; Bone Density*; Linear Models
  18. 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.
    MeSH terms: Animals; Base Sequence; Cell Line; Gene Expression Regulation*; Humans; Lipopolysaccharides/immunology; Macrophages/immunology; Macrophages/metabolism; Organ Specificity/genetics; RNA/genetics*; RNA/chemistry; Signal Transduction*; NF-kappa B/metabolism; Intercellular Adhesion Molecule-1/genetics*; Evolution, Molecular; ras Guanine Nucleotide Exchange Factors/genetics*; ras Guanine Nucleotide Exchange Factors/chemistry; RNA Stability; Protein Transport; Toll-Like Receptor 4/metabolism*; Mice
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