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  1. Tan AKG, Yen ST, Fang X, Chiang FS
    Int Health, 2019 03 01;11(2):150-158.
    PMID: 30321364 DOI: 10.1093/inthealth/ihy072
    BACKGROUND: This study examined the factors associated with body mass index (BMI) categories of Malaysian adolescents by physical activity (PA) status.

    METHODS: Data were obtained from the 2012 Malaysia Global School-based Student Health Survey. Generalized ordered logit regression analysis was conducted on 24 339 adolescents by PA status.

    RESULTS: Early- (ages 11-13) and middle-stage (ages 14-16) adolescents were associated with higher overweight and obesity risks than their older peers (ages 17-18). Male adolescents faced higher underweight and obesity likelihoods than females. Hunger due to food shortage at home was associated with higher likelihoods of underweight and normal weight BMI categories. Smokers were more likely to be underweight or normal weight than non-smokers. Segmented-sample analysis by PA status indicated that, while the direction of associations was parallel across PA status, the magnitudes of association between age, hunger and smoking status with BMI status were greater among active than inactive adolescents.

    CONCLUSIONS: Male adolescents faced a dual burden of underweight and obesity. Other sociodemographic and dietary-lifestyle factors were associated with adolescent BMI categories. Segmented-sample analysis by PA status uncovered varying associations between factors that would otherwise be masked in pooled sample analysis. Public health authorities should take these factors into consideration when deliberating programs to ensure healthy adolescent body weight.

  2. Tan LP, Foong KK, Yvonne Ai LL
    Med J Malaysia, 2018 10;73(5):334-335.
    PMID: 30350818 MyJurnal
    Amebiasis is one of the major causes of diarrhea in the developing countries and it can present with a wide range of gastrointestinal symptoms depending on the phase of infection. We described a case of 50 year-old male patient who presented with abdominal pain, diarrhea and vomiting. After right hemicolectomy for appendicular abscess with tumour over the ileum, histopathological examinations revealed numerous trophozoites of Entamoeba histolytica in a background of inflammations (Figure 1). Following resection of the ameboma, he received intravenous metronidazole treatment for total of two weeks duration.
  3. Farrukh MJ, Makmor-Bakry M, Hatah E, Tan HJ
    Patient Prefer Adherence, 2018;12:2111-2121.
    PMID: 30349205 DOI: 10.2147/PPA.S179031
    Purpose: To identify the use pattern of complementary and alternative medicine (CAM) and its impact on antiepileptic drug (AED) adherence among patients with epilepsy.

    Method: Potential studies were identified through a systematic search of Scopus, Science Direct, Google Scholar, and PubMed. The keywords used to identify relevant articles were "adherence," "AED," "epilepsy," "non-adherence," and "complementary and alternative medicine." An article was included in the review if the study met the following criteria: 1) conducted in epilepsy patients, 2) conducted in patients aged 18 years and above, 3) conducted in patients prescribed AEDs, and 4) patients' adherence to AEDs.

    Results: A total of 3,330 studies were identified and 30 were included in the final analysis. The review found that the AED non-adherence rate reported in the studies was between 25% and 66%. The percentage of CAM use was found to be between 7.5% and 73.3%. The most common reason for inadequate AED therapy and higher dependence on CAM was the patients' belief that epilepsy had a spiritual or psychological cause, rather than primarily being a disease of the brain. Other factors for AED non-adherence were forgetfulness, specific beliefs about medications, depression, uncontrolled recent seizures, and frequent medication dosage.

    Conclusion: The review found a high prevalence of CAM use and non-adherence to AEDs among epilepsy patients. However, a limited number of studies have investigated the association between CAM usage and AED adherence. Future studies may wish to explore the influence of CAM use on AED medication adherence.

  4. Ng KT, Chan XL, Tan W, Wang CY
    J Clin Anesth, 2019 Feb;52:37-47.
    PMID: 30172838 DOI: 10.1016/j.jclinane.2018.08.019
    OBJECTIVES: Patients with preoperative low left ventricular ejection fraction (LVEF) are known to be associated with high morbidities and mortality in cardiac surgery. The primary aim of this review was to examine the clinical outcomes of levosimendan versus placebo in patients with preoperative low LVEF ≤ 50% undergoing cardiac surgery.

    DATA SOURCES: MEDLINE, EMBASE, PubMed and CENTRAL were searched systematically from their inception until June 2018.

    REVIEW METHODS: All the randomised clinical trials (RCTs) were included.

    RESULTS: Twelve trials were eligible (n = 1867) for inclusion in the data synthesis. In comparison to the placebo cohort, the levosimendan cohort showed a significant reduction in mortality (TSA = inconclusive; ρ = 0.002; I2 = 0%; FEM: OR 0.56; 95% CI 0.39, 0.80), especially in the subgroups of preoperative severe low LVEF ≤ 30% (ρ = 0.003; OR 0.33; 95% CI 0.16, 0.69), preoperative administering of levosimendan (ρ = 0.001; OR 0.46; 95% CI 0.29, 0.74) and patients who had bolus followed by infusion of levosimendan (ρ = 0.005; OR 0.50; 95% CI 0.30, 0.81). However, the effect on mortality was not significant in the subgroup analysis of high quality trials (ρ = 0.14; OR 0.73; 95% CI 0.47, 1.12). The levosimendan cohort showed a significantly lower incidence of low-cardiac-output-syndrome (ρ 

  5. Puah SM, Tan JAMA, Chew CH, Chua KH
    J Food Sci, 2018 Sep;83(9):2337-2342.
    PMID: 30101982 DOI: 10.1111/1750-3841.14300
    Staphylococcus aureus is able to form multilayer biofilms embedded within a glycocalyx or slime layer. Biofilm formation poses food contamination risks and can subsequently increase the risk of food poisoning. Identification of food-related S. aureus strains will provide additional data on staphylococcal food poisoning involved in biofilm formation. A total of 52 S. aureus strains isolated from sushi and sashimi was investigated to study their ability for biofilm formation using crystal violet staining. The presence of accessory gene regulator (agr) groups and 15 adhesion genes was screened and their associations in biofilm formation were studied. All 52 S. aureus strains showed biofilm production on the tested hydrophobic surface with 44% (23/52) strains classified as strong, 33% (17/52) as moderate, and 23% (12/52) as weak biofilm producers. The frequency of agr-positive strains was 71% (agr group 1 = 21 strains; agr group 2 = 2 strains; agr group 3 = 12 strains; agr group 4 = 2 strains) whereas agr-negative strains were 29% (15/52). Twelve adhesion genes were detected and 98% of the S. aureus strains carried at least one adhesion gene. The ebps was significantly (p < .05) associated with strong biofilm producing strains. In addition, eno, clfA, icaAD, sasG, fnbB, cna, and sasC were significantly higher in the agr-positive group compared to the agr-negative group. The results of this study suggest that the presence of ebps, eno, clfA, icaAD, sasG, fnbB, cna, and sasC may play an important role in enhancing the stage of biofilm-related infections and warrants further investigation.

    PRACTICAL APPLICATION: This work contributes to the knowledge on the biofilm formation and the distribution of agr groups in S. aureus strains as well as microbial surface components in recognizing adherence matrix molecules of organisms isolated from ready-to-eat sushi and sashimi. The findings provide valuable information to further study the roles of specific genes in causing biofilm-related infections.

  6. Liao SJ, Chong MC, Tan MP, Chua YP
    Geriatr Nurs, 2018 08 31;40(2):154-159.
    PMID: 30173939 DOI: 10.1016/j.gerinurse.2018.08.001
    Depression leads to a poorer quality of life (QOL) which is a determinant of healthy ageing. Cost-effective solutions for enhancing QOL in the older population are much needed in China, with its rapidly ageing population. We conducted a randomized controlled trial involving 112 community-dwelling older participants with mild to moderate depression, to evaluate the effect of Tai Chi with music on QOL (57 in intervention group, 55 in control group). WHO Quality of Life-BREF was used to measure QOL at baseline and at every month for three months. Following the adjustments for sociodemographic data, the effect of intervention on QOL was assured (F = 25.145, P 
  7. Tan SMQ, Chiew Y, Ahmad B, Kadir KA
    Nutrients, 2018 Sep 17;10(9).
    PMID: 30227659 DOI: 10.3390/nu10091315
    Tocotrienol-rich vitamin E from palm oil (Tocovid) has been shown to ameliorate diabetes through its superior antioxidant, antihyperglycemic, and anti-inflammatory properties in diabetic rats. This study aimed to investigate the effects of Tocovid on diabetic nephropathy in patients with type 2 diabetes. Baseline parameters of potential subjects such as HbA1c, blood pressure, Advanced Glycation Endproduct (AGE), soluble receptor for AGE (sRAGE), Nε-Carboxymethyllysine (Nε-CML), and Cystatin C were assessed for possible correlation with diabetic nephropathy. Only subjects with diabetic nephropathy or urine microalbuminuria-positive defined as Urine Albumin to Creatinine Ratio (UACR) >10 mg/mmol were recruited into a prospective, randomized, double-blinded, placebo-controlled trial. The intervention group (n = 22) received Tocovid 200 mg twice a day while the control group (n = 23) received placebo twice a day for 8 weeks. Changes in Hemoglobin A1c (HbA1c), blood pressure, serum biomarkers and renal parameters such as UACR, serum creatinine, and estimated Glomerular Filtration Rate (eGFR) were compared between the two groups. It was found that serum Nε-CML significantly correlated to the severity of microalbuminuria. For every 1 ng/mL increase in serum Nε-CML, the odds of diabetic nephropathy increased by 1.476 times. Tocovid, compared to placebo, significantly reduced serum creatinine but not eGFR, UACR, HbA1c, blood pressure, and serum biomarkers. In conclusion, serum Nε-CML is a potential biomarker for diabetic nephropathy. Treatment with Tocovid significantly reduced serum creatinine; therefore Tocovid may be a useful addition to the current treatment for diabetic nephropathy.
  8. Tan SK, Tang ATH, Leung WK, Zwahlen RA
    J Stomatol Oral Maxillofac Surg, 2018 Dec;119(6):461-468.
    PMID: 30099221 DOI: 10.1016/j.jormas.2018.07.004
    PURPOSE: To investigate short- and long-term post-surgical three-dimensional changes of pharyngeal airway morphology and hyoid bone position in dento-skeletal class II deformity patients after two-jaw surgery with segmentation.

    METHODS: Relations between skeletal movement, hyoid bone position and three-dimensional pharyngeal airway changes were retrospectively analyzed on pre- and post-surgical CBCTs in dento-skeletal class II patients who underwent orthognathic two-jaw surgery with segmentation.

    RESULTS: While long-term significant reductions in length (P= 0.003), surface area (P= 0.042) and volume (P= 0.004) were found in the nasopharynx, the highly significant increases in oropharyngeal airway length, surface area, volume and the minimal cross-sectional area (P 

  9. Tan CSY, Fong AYY, Jong YH, Ong TK
    Glob Heart, 2018 12;13(4):241-244.
    PMID: 30213574 DOI: 10.1016/j.gheart.2018.08.003
    BACKGROUND: Warfarin is an anticoagulant indicated for patients who had undergone mechanical heart valve(s) replacement (MHVR). In these patients, time in therapeutic range (TTR) is important in predicting the bleeding and thrombotic risks.
    OBJECTIVE: This study aimed to describe the anticoagulation control of warfarin using TTR in patients with MHVR in a tertiary health care referral Center.
    METHODS: Data were collected retrospectively by reviewing clinical notes of outpatients who attended international normalized ratio (INR) clinics in November 2015. Patients who had MHVR and who took warfarin were included. The data collected were demographics, relevant laboratory investigations, and patients' prior medical history. TTR was calculated using Rosendaal and traditional methods.
    RESULTS: A total of 103 patients with MHVR were recruited. The mean age was 51.72 ± 13.97 years and 46.6% were male. A total of 54.4% had mitral valve replacement (MVR), whereas 26.2% had aortic valve replacement (AVR). The mean TTR calculated using the Rosendaal method was 57.1%. There was no significant difference among patients with AVR, MVR, and both valves (AMVR) in terms of TTR (AVR vs. MVR vs. AMVR, 62.94 ± 23.08, 54.12 ± 21.62, 57.63 ± 17.47; p = 0.213). The average dose of warfarin for all groups was approximately 3 mg/day. Moreover, MVR, AVR, and AMVR patients who had TTR (Rosendaal method) ≤60% were 58.9%, 37.0%, and 45.0%, respectively. Only 4.8% had minor bleeding, whereas none had stroke in the period of TTR determination.
    CONCLUSIONS: Despite a majority of patients having <60% TTR, there were low incidences of bleeding and stroke events in this center. There were no factors found to be associated with INR control in this study.
    Study site: INR clinic, Sarawak Heart Centre, Sarawak General Hospital, Malaysia
  10. Yıldırım Ö, Pławiak P, Tan RS, Acharya UR
    Comput Biol Med, 2018 11 01;102:411-420.
    PMID: 30245122 DOI: 10.1016/j.compbiomed.2018.09.009
    This article presents a new deep learning approach for cardiac arrhythmia (17 classes) detection based on long-duration electrocardiography (ECG) signal analysis. Cardiovascular disease prevention is one of the most important tasks of any health care system as about 50 million people are at risk of heart disease in the world. Although automatic analysis of ECG signal is very popular, current methods are not satisfactory. The goal of our research was to design a new method based on deep learning to efficiently and quickly classify cardiac arrhythmias. Described research are based on 1000 ECG signal fragments from the MIT - BIH Arrhythmia database for one lead (MLII) from 45 persons. Approach based on the analysis of 10-s ECG signal fragments (not a single QRS complex) is applied (on average, 13 times less classifications/analysis). A complete end-to-end structure was designed instead of the hand-crafted feature extraction and selection used in traditional methods. Our main contribution is to design a new 1D-Convolutional Neural Network model (1D-CNN). The proposed method is 1) efficient, 2) fast (real-time classification) 3) non-complex and 4) simple to use (combined feature extraction and selection, and classification in one stage). Deep 1D-CNN achieved a recognition overall accuracy of 17 cardiac arrhythmia disorders (classes) at a level of 91.33% and classification time per single sample of 0.015 s. Compared to the current research, our results are one of the best results to date, and our solution can be implemented in mobile devices and cloud computing.
  11. Chuah FLH, Tan ST, Yeo J, Legido-Quigley H
    Int J Equity Health, 2018 08 15;17(1):120.
    PMID: 30111329 DOI: 10.1186/s12939-018-0833-x
    BACKGROUND: In Malaysia, refugees and asylum-seekers are a vulnerable group that often face circumstances in which their health and wellbeing can be compromised. This qualitative study sought to examine the key health concerns and barriers to healthcare access among refugees and asylum-seekers in Malaysia through the lens of healthcare professionals, program staff and experts on refugee and migrant health.

    METHODS: We conducted 20 semi-structured in-depth interviews with experts, healthcare professionals, program managers or executives from UN agencies, public healthcare facilities, civil society organizations, and academic institutions in Malaysia. Interviews were transcribed and analyzed both deductively and inductively using thematic analysis.

    RESULTS: Participant narratives highlight that the health needs of refugees and asylum-seekers in Malaysia are complex. As reported, access to healthcare is underpinned by numerous social, cultural and economic determinants compounded by a legal environment that lacks inclusivity of refugees and asylum-seekers. Apart from the health risks associated with the migration process, limited access to comprehensive healthcare post-arrival remain a problem for refugees and asylum-seekers in Malaysia. Key barriers to healthcare access are linked to poor health literacy and the lack of awareness on one's right to healthcare; language and cultural differences; protection issues resulting from a lack of legal status; and an inability to afford healthcare due to inadequate livelihoods. Overall, poor access to healthcare is perceived to have detrimental consequences on the health status of refugees, asylum-seekers and its host population, and may incur greater costs to the health system in the long run.

    CONCLUSION: Comprehensive efforts in practice and research that tackle the social, cultural and economic determinants of health, and more inclusive health policies are crucial in strengthening healthcare access among refugees and asylum-seekers in Malaysia. Practical recommendations include improving the health literacy of refugees and asylum-seekers for better navigation of the health system; bridging language and cultural gaps through translation support and inter-cultural orientation; implementing policies grounded in the right to healthcare for all regardless of legal status and in the interest of public health; and establishing a larger evidence base to drive policy development and implementation for refugee health within the Malaysian context.

  12. Sulaiman I, Tan K, Mohtarrudin N, Lim JCW, Stanslas J
    Pulm Pharmacol Ther, 2018 12;53:39-51.
    PMID: 30244166 DOI: 10.1016/j.pupt.2018.09.008
    Toluene diisocyanate (TDI) is a major cause of chemical-induced occupational asthma, which contributes about 15% of global asthma burden. Resistance and compounded side effects associated with the use of corticosteroid in asthma necessitate the search for alternative drugs. Andrographolide (AGP), a naturally occurring diterpene lactone is known to exhibit various bioactivities. Its ability to ameliorate cardinal features of allergic asthma was previously suggested in an eosinophilic asthma endotype. However, its potential antiasthma activity and mechanism of action in a neutrophilic occupational asthma model, as well as its effect on epithelial dysfunction remain unknown. BALB/c mice were dermally sensitised with 0.3% TDI or acetone olive oil (AOO) vehicle on day 1 and 8, followed by 0.1% TDI intranasal challenge on days 15, 18 and 21. Endpoints were evaluated via bronchoalveolar lavage fluid (BALF) cell analysis, 2',7'-dichlorofluorescein diacetate (DCFDA) assays, immunoblotting, immunohistochemistry and methacholine challenge test. Decreases in total and differential leukocyte counts of BALF were recorded in AGP-treated animals. The compound dose-dependently reduced intracellular de-esterification of DCFDA, thus suggesting AGP's potential to inhibit intracellular reactive oxygen species (ROS). Mechanistically, the treatment prevented TDI-induced aberrant E-cadherin distribution and restored airway epithelial β-catenin at cell to cell contact site. Furthermore, AGP ameliorated TDI induced pulmonary collagen deposition. In addition, the treatment significantly upregulated pulmonary HO-1, Nrf2 and phospho-p38 levels. Airway hyperresponsiveness was markedly suppressed among AGP-treated animals. Collectively, these findings suggest AGP's protective function against TDI-induced airway epithelial barrier dysfunction and oxidative lung damage possibly through the upregulation of adherence junction proteins and the activation of p38/Nrf2 signalling. This study elucidates the therapeutic potential of AGP in the control and management of chemical-induced allergic asthma. To the best of our knowledge, the potential anti-asthma activity of AGP in TDI-induced occupational asthma has not been reported previously.
  13. Abu Bakar MH, Azmi MN, Shariff KA, Tan JS
    Appl Biochem Biotechnol, 2019 May;188(1):241-259.
    PMID: 30417321 DOI: 10.1007/s12010-018-2920-2
    Withaferin A (WA), a bioactive constituent derived from Withania somnifera plant, has been shown to exhibit many qualifying properties in attenuating several metabolic diseases. The current investigation sought to elucidate the protective mechanisms of WA (1.25 mg/kg/day) on pre-existing obese mice mediated by high-fat diet (HFD) for 12 weeks. Following dietary administration of WA, significant metabolic improvements in hepatic insulin sensitivity, adipocytokines with enhanced glucose tolerance were observed. The hepatic oxidative functions of obese mice treated with WA were improved via augmented antioxidant enzyme activities. The levels of serum pro-inflammatory cytokines and hepatic mRNA expressions of toll-like receptor (TLR4), nuclear factor κB (NF-κB), tumor necrosis factor-α (TNF-α), chemokine (C-C motif) ligand-receptor, and cyclooxygenase 2 (COX2) in HFD-induced obese mice were reduced. Mechanistically, WA increased hepatic mRNA expression of peroxisome proliferator-activated receptors (PPARs), cluster of differentiation 36 (CD36), fatty acid synthase (FAS), carnitine palmitoyltransferase 1 (CPT1), glucokinase (GCK), phosphofructokinase (PFK), and phosphoenolpyruvate carboxykinase (PCK1) that were associated with enhanced lipid and glucose metabolism. Taken together, these results indicate that WA exhibits protective effects against HFD-induced obesity through attenuation of hepatic inflammation, oxidative stress, and insulin resistance in mice.
  14. Lian W, Wang W, Tan CP, Wang J, Wang Y
    Bioprocess Biosyst Eng, 2019 Feb;42(2):321-329.
    PMID: 30421172 DOI: 10.1007/s00449-018-2036-7
    LML-type structured lipids are one type of medium- and long-chain triacylglycerols. LML was synthesized using immobilized Talaromyces thermophilus lipase (TTL)-catalyzed interesterification of tricaprylin and ethyl linoleate. The resin AB-8 was chosen, and the lipase/support ratio was determined to be 60 mg/g. Subsequently, the immobilized TTL with strict sn-1,3 regiospecificity was applied to synthesize LML. Under the optimized conditions (60 °C, reaction time 6 h, enzyme loading of 6% of the total weight of substrates, substrate of molar ratio of ethyl linoleate to tricaprylin of 6:1), Triacylglycerols with two long- and one medium-chain FAs (DL-TAG) content as high as 52.86 mol% was obtained. Scale-up reaction further verified the industrial potential of the established process. The final product contained 85.24 mol% DL-TAG of which 97 mol% was LML after purification. The final product obtained with the high LML content would have substantial potential to be used as functional oils.
  15. Liang H, Qin X, Tan CP, Li D, Wang Y
    J Agric Food Chem, 2018 Nov 21;66(46):12361-12367.
    PMID: 30394748 DOI: 10.1021/acs.jafc.8b04804
    Docosahexaenoyl and eicosapentaenoyl ethanolamides (DHEA and EPEA) have physiological functions, including immunomodulation, brain development, and anti-inflammation, but their efficient production is still unresolved. In this study, choline-chloride-based natural deep eutectic solvents are used as media to improve the production of DHEA and EPEA. The water content showed a key effect on the reactant conversion. Adding water to choline chloride-glucose (CG, molar ratio of 5:2) led to a significant increase (13.03% for EPEA and 27.95% for DHEA) in the yields after 1 h. The high yields of EPEA (96.84%) and DHEA (90.06%) were obtained under the optimized conditions [fish oil ethyl esters/ethanolamine molar ratio of 1:2, temperature of 60 °C, 1 h, enzyme loading of 2195 units, and CG containing 8.50% water of 43.30% (w/w, relative to total reactants)]. The products could be easily separated using centrifugation. In summary, the research has the potential to produce fatty acyl ethanolamides.
  16. Thalha AM, Mahadeva S, Boon Tan AT, Mun KS
    JGH Open, 2018 Oct;2(5):242-245.
    PMID: 30483596 DOI: 10.1002/jgh3.12083
    A 33-year-old man was referred with hyperosmotic symptoms of 4 weeks. Clinical examination showed palpable hepatomegaly and no stigmata of liver disease. Findings were random glucose 16.6 mmol/L, HbA1c 12.4%, triglyceride 6.2 mmol/L, normal LFTs and ultrasound liver: increased echogenicity. Management consisted of dietician referral and commencement of metformin 500 mg bd, diamicron MR 60 mg od, and fenofibrate 145 mg od. He was non-compliant, complaining of "heaviness of head" after consuming oral diabetic agents, without symptoms of hypoglycemia. Treatment was switched to Kombiglyze XR (saxaglipitin 5 mg + metformin 1000 mg) and empagliflozin 25 mg od. He presented 1 week later with generalised pruritus with ALT 307 IU/L and serum GGT 808 IU/L. Following this, a percutaneous liver biopsy was performed, revealing steatohepatitis and marked intra-hepatic cholestasis. Kombiglyze XR was withheld, with resolution of LFTs to baseline. Phenotypes of liver injury are categorised according to R value, defined as ratio ALT/ULN:ALP/ULN. R value of ≥5:hepatocellular injury, ≤2:cholestatic injury, 2-5:mixed-type injury. Here, R value points toward mixed type (R = 3.203). Hepatotoxicity in patients with NASH is difficult to diagnose, based on laboratory parameters. Liver histology was useful in indicating additional changes apart from NASH, causing liver derangement. The Rousal Uclaf Causality Assessment Method is a scoring method to determine the probability of drug induced liver injury. RUCAM score for this case was 6 (probable adverse drug reaction). Hepatotoxicity from saxagliptin not been reported prior. Clinicians need to be more vigilant, particularly in patients with NASH.
  17. Tan SN, Sim SP, Khoo ASB
    BMC Mol. Biol., 2018 12 04;19(1):15.
    PMID: 30514321 DOI: 10.1186/s12867-018-0116-5
    BACKGROUND: Oxidative stress is known to be involved in most of the aetiological factors of nasopharyngeal carcinoma (NPC). Cells that are under oxidative stress may undergo apoptosis. We have previously demonstrated that oxidative stress-induced apoptosis could be a potential mechanism mediating chromosome breakages in nasopharyngeal epithelial cells. Additionally, caspase-activated DNase (CAD) may be the vital player in mediating the chromosomal breakages during oxidative stress-induced apoptosis. Chromosomal breakage occurs during apoptosis and chromosome rearrangement. Chromosomal breakages tend to cluster in certain regions, such as matrix association region/scaffold attachment region (MAR/SAR). We hypothesised that oxidative stress-induced apoptosis may result in chromosome breaks preferentially at the MAR/SAR sites. The AF9 gene at 9p22 was targeted in this study because 9p22 is a deletion site commonly found in NPC.

    RESULTS: By using MAR/SAR recognition signature (MRS), potential MAR/SAR sites were predicted in the AF9 gene. The predicted MAR/SAR sites precisely match to the experimentally determined MAR/SARs. Hydrogen peroxide (H2O2) was used to induce apoptosis in normal nasopharyngeal epithelial cells (NP69) and NPC cells (HK1). Nested inverse polymerase chain reaction was employed to identify the AF9 gene cleavages. In the SAR region, the gene cleavage frequency of H2O2-treated cells was significantly higher than that of the non-treated cells. A few chromosomal breakages were detected within the AF9 region which was previously found to be involved in the mixed lineage leukaemia (MLL)-AF9 translocation in an acute lymphoblastic leukaemia patient. As for the non-SAR region, no significant difference in the gene cleavage frequency was found between the untreated control and H2O2-treated cells. Furthermore, H2O2-induced cleavages within the SAR region were reduced by caspase-3 inhibitor, which indirectly inhibits CAD.

    CONCLUSIONS: These results reaffirm our previous findings that oxidative stress-induced apoptosis could be one of the potential mechanisms underlying chromosome breakages in nasopharyngeal epithelial cells. MAR/SAR may play a vital role in defining the location of chromosomal breakages mediated by oxidative stress-induced apoptosis, where CAD is the major nuclease.

  18. Fu TL, Ong KC, Tan SH, Wong KT
    J. Neuropathol. Exp. Neurol., 2019 12 01;78(12):1160-1170.
    PMID: 31675093 DOI: 10.1093/jnen/nlz103
    Japanese encephalitis (JE) is a known CNS viral infection that often involves the thalamus early. To investigate the possible role of sensory peripheral nervous system (PNS) in early neuroinvasion, we developed a left hindlimb footpad-inoculation mouse model to recapitulate human infection by a mosquito bite. A 1-5 days postinfection (dpi) study, demonstrated focal viral antigens/RNA in contralateral thalamic neurons at 3 dpi in 50% of the animals. From 4 to 5 dpi, gradual increase in viral antigens/RNA was observed in bilateral thalami, somatosensory, and piriform cortices, and then the entire CNS. Infection of neuronal bodies and adjacent nerves in dorsal root ganglia (DRGs), trigeminal ganglia, and autonomic ganglia (intestine, etc.) was also observed from 5 dpi. Infection of explant organotypic whole brain slice cultures demonstrated no viral predilection for the thalamus, while DRG and intestinal ganglia organotypic cultures confirmed sensory and autonomic ganglia susceptibility to infection, respectively. Early thalamus and sensory-associated cortex involvement suggest an important role for sensory pathways in neuroinvasion. Our results suggest that JE virus neuronotropism is much more extensive than previously known, and that the sensory PNS and autonomic system are susceptible to infection.
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