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  1. Fulltext Transcriptome analysis of chicken intraepithelial lymphocyte natural killer cells infected with very virulent infectious bursal disease virus
    Boo SY, Tan SW, Alitheen NB, Ho CL, Omar AR, Yeap SK
    Sci Rep, 2020 10 27;10(1):18348.
    PMID: 33110122 DOI: 10.1038/s41598-020-75340-x
    The infectious bursal disease (IBD) is an acute immunosuppressive viral disease that significantly affects the economics of the poultry industry. The IBD virus (IBDV) was known to infect B lymphocytes and activate macrophage and T lymphocytes, but there are limited studies on the impact of IBDV infection on chicken intraepithelial lymphocyte natural killer (IEL-NK) cells. This study employed an mRNA sequencing approach to investigate the early regulation of gene expression patterns in chicken IEL-NK cells after infection with very virulent IBDV strain UPM0081. A total of 12,141 genes were expressed in uninfected chicken IEL-NK cells, and most of the genes with high expression were involved in the metabolic pathway, whereas most of the low expressed genes were involved in the cytokine-cytokine receptor pathway. A total of 1,266 genes were differentially expressed (DE) at 3 day-post-infection (dpi), and these DE genes were involved in inflammation, antiviral response and interferon stimulation. The innate immune response was activated as several genes involved in inflammation, antiviral response and recruitment of NK cells to the infected area were up-regulated. This is the first study to examine the whole transcriptome profile of chicken NK cells towards IBDV infection and provides better insight into the early immune response of chicken NK cells.
  2. Fulltext Integrated Stirred-Tank Bioreactor with Internal Adsorption for the Removal of Ammonium to Enhance the Cultivation Performance of gdhA Derivative Pasteurella multocida B:2
    Oslan SNH, Tan JS, Abbasiliasi S, Ziad Sulaiman A, Saad MZ, Halim M, et al.
    Microorganisms, 2020 Oct 24;8(11).
    PMID: 33114463 DOI: 10.3390/microorganisms8111654
    Growth of mutant gdhA Pasteurella multocida B:2 was inhibited by the accumulation of a by-product, namely ammonium in the culture medium during fermentation. The removal of this by-product during the cultivation of mutant gdhA P. multocida B:2 in a 2 L stirred-tank bioreactor integrated with an internal column using cation-exchange adsorption resin for the improvement of cell viability was studied. Different types of bioreactor system (dispersed and internal) with resins were successfully used for ammonium removal at different agitation speeds. The cultivation in a bioreactor integrated with an internal column demonstrated a significant improvement in growth performance of mutant gdhA P. multocida B:2 (1.05 × 1011 cfu/mL), which was 1.6-fold and 8.4-fold as compared to cultivation with dispersed resin (7.2 × 1010 cfu/mL) and cultivation without resin (1.25 × 1010 cfu/mL), respectively. The accumulation of ammonium in culture medium without resin (801 mg/L) was 1.24-fold and 1.37-fold higher than culture with dispersed resin (642.50 mg/L) and culture in the bioreactor integrated with internal adsorption (586.50 mg/L), respectively. Results from this study demonstrated that cultivation in a bioreactor integrated with the internal adsorption column in order to remove ammonium could reduce the inhibitory effect of this by-product and improve the growth performance of mutant gdhA P. multocida B:2.
  3. Fulltext Catalpol Ameliorates Insulin Sensitivity and Mitochondrial Respiration in Skeletal Muscle of Type-2 Diabetic Mice Through Insulin Signaling Pathway and AMPK/SIRT1/PGC-1α/PPAR-γ Activation
    Yap KH, Yee GS, Candasamy M, Tan SC, Md S, Abdul Majeed AB, et al.
    Biomolecules, 2020 09 24;10(10).
    PMID: 32987623 DOI: 10.3390/biom10101360
    Catalpol was tested for various disorders including diabetes mellitus. Numerous molecular mechanisms have emerged supporting its biological effects but with little information towards its insulin sensitizing effect. In this study, we have investigated its effect on skeletal muscle mitochondrial respiration and insulin signaling pathway. Type-2 diabetes (T2DM) was induced in male C57BL/6 by a high fat diet (60% Kcal) and streptozotocin (50 mg/kg, i.p.). Diabetic mice were orally administered with catalpol (100 and 200 mg/kg), metformin (200 mg/kg), and saline for four weeks. Fasting blood glucose (FBG), HbA1c, plasma insulin, oral glucose tolerance test (OGTT), insulin tolerance test (ITT), oxygen consumption rate, gene (IRS-1, Akt, PI3k, AMPK, GLUT4, and PGC-1α) and protein (AMPK, GLUT4, and PPAR-γ) expression in muscle were measured. Catalpol (200 mg/kg) significantly (p < 0.05) reduced the FBG, HbA1C, HOMA_IR index, and AUC of OGTT whereas, improved the ITT slope. Gene (IRS-1, Akt, PI3k, GLUT4, AMPK, and PGC-1α) and protein (AMPK, p-AMPK, PPAR-γ and GLUT4) expressions, as well as augmented state-3 respiration, oxygen consumption rate, and citrate synthase activity in muscle was observed in catalpol treated mice. The antidiabetic activity of catalpol is credited with a marked improvement in insulin sensitivity and mitochondrial respiration through the insulin signaling pathway and AMPK/SIRT1/PGC-1α/PPAR-γ activation in the skeletal muscle of T2DM mice.
  4. Fulltext De novo transcriptome analysis of Chlorella sorokiniana: effect of glucose assimilation, and moderate light intensity
    Azaman SNA, Wong DCJ, Tan SW, Yusoff FM, Nagao N, Yeap SK
    Sci Rep, 2020 Oct 15;10(1):17331.
    PMID: 33060668 DOI: 10.1038/s41598-020-74410-4
    Chlorella can produce an unusually wide range of metabolites under various nutrient availability, carbon source, and light availability. Glucose, an essential molecule for the growth of microorganisms, also contributes significantly to the metabolism of various metabolic compounds produced by Chlorella. In addition, manipulation of light intensity also induces the formation of secondary metabolites such as pigments, and carotenoids in Chlorella. This study will focus on the effect of glucose addition, and moderate light on the regulation of carotenoid, lipid, starch, and other key metabolic pathways in Chlorella sorokiniana. To gain knowledge about this, we performed transcriptome profiling on C. sorokiniana strain NIES-2168 in response to moderate light stress supplemented with glucose under mixotrophic conditions. A total of 60,982,352 raw paired-end (PE) reads 100 bp in length was obtained from both normal, and mixotrophic samples of C. sorokiniana. After pre-processing, 93.63% high-quality PE reads were obtained, and 18,310 predicted full-length transcripts were assembled. Differential gene expression showed that a total of 937, and 1124 genes were upregulated, and downregulated in mixotrophic samples, respectively. Transcriptome analysis revealed that the mixotrophic condition caused upregulation of genes involved in carotenoids production (specifically lutein biosynthesis), fatty acid biosynthesis, TAG accumulation, and the majority of the carbon fixation pathways. Conversely, starch biosynthesis, sucrose biosynthesis, and isoprenoid biosynthesis were downregulated. Novel insights into the pathways that link the enhanced production of valuable metabolites (such as carotenoids in C. sorokiniana) grown under mixotrophic conditions is presented.
  5. Fulltext Postpartum women's perception of antenatal breastfeeding education: a descriptive survey
    Tan ML, Foong SC, Ho JJ, Foong WC, Mohd R, Harun Z
    Int Breastfeed J, 2020 10 14;15(1):85.
    PMID: 33054789 DOI: 10.1186/s13006-020-00328-2
    BACKGROUND: Antenatal breastfeeding education (ANBE) is provided to all pregnant women attending Ministry of Health (MOH) clinics and some private health facilities in Malaysia, in line with the WHO/UNICEF Baby-Friendly Hospital Initiative (BFHI). However, the 6 month exclusive breastfeeding prevalence remains relatively low in Malaysia, suggesting that there may be a gap between what is currently taught and what is received by the women.

    OBJECTIVES: To determine how women perceived their ANBE experience in the first 8 weeks postpartum including what was useful and what they would like to have been included, sources of ANBE and infant feeding practices at the time of survey.

    METHODS: Women during their first 8 weeks postpartum who attended MOH clinics in Penang State, Malaysia were surveyed using a self-administered questionnaire in April and May 2015. Categorical responses were presented as numbers and proportions while free text responses were compiled verbatim and categorised into themes. The perceptions of primiparous and multiparous women were compared. Multivariate logistic regression adjusted to known confounders was used to determine if ANBE was associated with exclusive breastfeeding at the time of survey.

    RESULTS: A total of 421 women completed the 15-item questionnaire (84% response rate) of which 282 were complete and available for analysis. Of these, 95% had received ANBE, majority (88%) from MOH clinics. Almost all women found it useful. However, there were areas both in the delivery (e.g. too short) and the content (e.g. nothing new) that were described as not useful; and areas they would like more coverage (e.g. milk expression, storage and overcoming low milk supply). The exclusive breastfeeding prevalence at the time of survey was 61%. ANBE was significantly associated with exclusive breastfeeding even after adjusting for confounders (adjusted odds ratio [aOR] 8.1, 95% confidence interval 1.7, 38.3).

    CONCLUSIONS: ANBE is widely implemented and perceived as useful and may be associated with exclusive breastfeeding. Our findings give insight into content that women would like more of and how delivery of ANBE could be improved, including individualized sessions and communicating at a suitable level and language. Future studies could focus on the quality of ANBE delivery.

  6. Fulltext Jejunojejunal intussusception secondary to inflammatory fibroid polyp: A rare cause of small bowel obstruction
    Tan JS, Teah KM, Hoe VC, Khairuddin A, Sellapan H, Hayati F, et al.
    Ann Med Surg (Lond), 2020 Nov;59:251-253.
    PMID: 33088499 DOI: 10.1016/j.amsu.2020.10.009
    Background: Adult intussusception is a relatively rare clinical entity. The majority of cases of intussusception in adults are due to a pathologic condition that serves as a lead point and requires surgery. Small bowel intussusception is usually caused by benign or malignant neoplasms appearing at the head of the invagination. Inflammatory fibroid polyp (IFP) of the small bowel is an unusual benign neoplastic lesion that has been rarely reported to cause intussusception, especially in the jejunum.

    Case presentation: We present a rare case of adult intussusception who presented with a triad of intestinal obstruction. Computed tomography revealed small bowel intussusception with bowel ischemia. Intraoperatively, she required resection of the small bowel and primary anastomosis. Macroscopic examination revealed a single pedunculated polyp, which is the lead point of intestinal obstruction and confirmed histologically.

    Conclusion: Inflammatory fibroid polyp should be considered as a cause of intussusception among adults with small bowel obstruction.

  7. Fulltext Advances in the Diagnosis of Foot-and-Mouth Disease
    Wong CL, Yong CY, Ong HK, Ho KL, Tan WS
    Front Vet Sci, 2020;7:477.
    PMID: 32974392 DOI: 10.3389/fvets.2020.00477
    Foot-and-mouth disease (FMD) is a devastating livestock disease caused by foot-and-mouth disease virus (FMDV). Outbreaks of this disease in a country always result in conspicuous economic losses to livestock industry and subsequently lead to serious socioeconomic damages due to the immediate imposition of trade embargo. Rapid and accurate diagnoses are imperative to control this infectious virus. In the current review, enzyme-linked immunosorbent assay (ELISA)-based methods used in FMD diagnosis are extensively reviewed, particularly the sandwich, liquid-phase blocking, and solid-phase competition ELISA. The differentiation of infected animals from vaccinated animals using ELISA-based methods is also highlighted, in which the role of 3ABC polyprotein as a marker is reviewed intensively. Recently, more studies are focusing on the molecular diagnostic methods, which detect the viral nucleic acids based on reverse transcription-polymerase chain reaction (RT-PCR) and RT-loop-mediated isothermal amplification (RT-LAMP). These methods are generally more sensitive because of their ability to amplify a minute amount of the viral nucleic acids. In this digital era, the RT-PCR and RT-LAMP are progressing toward the mobile versions, aiming for on-site FMDV diagnosis. Apart from RT-PCR and RT-LAMP, another diagnostic assay specifically designed for on-site diagnosis is the lateral flow immunochromatographic test strips. These test strips have some distinct advantages over other diagnostic methods, whereby the assay often does not require the aid of an external device, which greatly lowers the cost per test. In addition, the on-site diagnostic test can be easily performed by untrained personnel including farmers, and the results can be obtained in a few minutes. Lastly, the use of FMDV diagnostic assays for progressive control of the disease is also discussed critically.
  8. Cellular uptake and anti-inflammatory effects of palm oil-derived delta (δ)-tocotrienol in microglia
    Tan SW, Israf Ali DAB, Khaza'ai H, Wong JW, Vidyadaran S
    Cell Immunol, 2020 11;357:104200.
    PMID: 32979761 DOI: 10.1016/j.cellimm.2020.104200
    Tocopherols long dominated studies on vitamin E, although interest has shifted to tocotrienols. It was previously shown that δ-tocotrienol derived from palm oil reduced nitric oxide released by BV2 microglia as early as 18 h after lipopolysaccharide stimulation. The current study measured δ-tocotrienol uptake by BV2 over a 24 h incubation period and its anti-inflammatory effects on primary microglia. Uptake of 17.5 μg/mL δ-tocotrienol by BV2 microglia began as early as 5 min and rose steeply to 21 ± 3% of the amount administered at 24 h. The amount of δ-tocotrienol retained in the lipopolysaccharide-stimulated microglia at 24 h was 14 ± 2%, with no substantial difference seen in unstimulated microglia. The same δ-tocotrienol regimen reduced nitric oxide levels by 82% at 24 h after lipopolysaccharide stimulation (p 
  9. Fulltext Exploring the Role of Gut Bacteria in Health and Disease in Preterm Neonates
    Lee JK, Hern Tan LT, Ramadas A, Ab Mutalib NS, Lee LH
    Int J Environ Res Public Health, 2020 09 23;17(19).
    PMID: 32977611 DOI: 10.3390/ijerph17196963
    The mortality rate of very preterm infants with birth weight <1500 g is as high as 15%. The survivors till discharge have a high incidence of significant morbidity, which includes necrotising enterocolitis (NEC), early-onset neonatal sepsis (EONS) and late-onset neonatal sepsis (LONS). More than 25% of preterm births are associated with microbial invasion of amniotic cavity. The preterm gut microbiome subsequently undergoes an early disruption before achieving bacterial maturation. It is postulated that bacterial gut colonisation at birth and postnatal intestinal dysbacteriosis precede the development of NEC and LONS in very preterm infants. In fact, bacterial colonization patterns in preterm infants greatly differ from term infants due to maternal chorioamnionitis, gestational age, delivery method, feeding type, antibiotic exposure and the environment factor in neonatal intensive care unit (NICU). In this regard, this review provides an overview on the gut bacteria in preterm neonates' meconium and stool. More than 50% of preterm meconium contains bacteria and the proportion increases with lower gestational age. Researchers revealed that the gut bacterial diversity is reduced in preterm infants at risk for LONS and NEC. Nevertheless, the association between gut dysbacteriosis and NEC is inconclusive with regards to relative bacteria abundance and between-sample beta diversity indices. With most studies show a disruption of the Proteobacteria and Firmicutes preceding the NEC. Hence, this review sheds light on whether gut bacteria at birth either alone or in combination with postnatal gut dysbacteriosis are associated with mortality and the morbidity of LONS and NEC in very preterm infants.
  10. Influence of Culture Conditions and Medium Compositions on the Production of Bacteriocin-Like Inhibitory Substances by Lactococcus lactis Gh1
    Jawan R, Abbasiliasi S, Tan JS, Mustafa S, Halim M, Ariff AB
    Microorganisms, 2020 Sep 23;8(10).
    PMID: 32977375 DOI: 10.3390/microorganisms8101454
    Antibacterial peptides or bacteriocins produced by many strains of lactic acid bacteria have been used as food preservatives for many years without any known adverse effects. Bacteriocin titres can be modified by altering the physiological and nutritional factors of the producing bacterium to improve the production in terms of yield and productivity. The effects of culture conditions (initial pH, inoculum age and inoculum size) and medium compositions (organic and inorganic nitrogen sources; carbon sources) were assessed for the production of bacteriocin-like inhibitory substances (BLIS) by Lactococcus lactis Gh1 in shake flask cultures. An inoculum of the mid-exponential phase culture at 1% (v/v) was the optimal age and size, while initial pH of culture media at alkaline and acidic state did not show a significant impact on BLIS secretion. Organic nitrogen sources were more favourable for BLIS production compared to inorganic sources. Production of BLIS by L. lactis Gh1 in soytone was 1.28-times higher as compared to that of organic nitrogen sources ((NH4)2SO4). The highest cell concentration (XmX = 0.69 ± 0.026 g·L-1) and specific growth rate (μmax = 0.14 h-1) were also observed in cultivation using soytone. By replacing carbon sources with fructose, BLIS production was increased up to 34.94% compared to BHI medium, which gave the biomass cell concentration and specific growth rate of 0.66 ± 0.002 g·L-1 and 0.11 h-1, respectively. It can be concluded that the fermentation factors have pronounced influences on the growth of L. lactis Gh1 and BLIS production. Results from this study could be used for subsequent application in process design and optimisation for improving BLIS production by L. lactis Gh1 at larger scale.
  11. Fulltext Investigation on the Curvature Correction Factor of Extension Spring
    Tan PS, Akhavan Farid A, Karimzadeh A, Rahimian Koloor SS, Petrů M
    Materials (Basel), 2020 Sep 21;13(18).
    PMID: 32967330 DOI: 10.3390/ma13184199
    The curvature correction factor is an important parameter in the stress calculation formulation of a helical extension spring, which describes the effect of spring wire curvature on the stress increase towards its inner radius. In this study, the parameters affecting the curvature correction factor were investigated through theoretical and numerical methods. Several finite element (FE) models of an extension spring were generated to obtain the distribution of the tensile stress in the spring. In this investigation, the hook orientation and the number of coils of the extension spring showed significant effects on the curvature correction factor. These parameters were not considered in the theoretical model for the calculation of the curvature correction factor, causing a deviation between the results of the FE model and the theoretical approach. A set of equations is proposed for the curvature correction factor, which relates both the spring index and the number of coils. These equations can be applied directly to the design of extension springs with a higher safety factor.
  12. Fulltext The Role of Breast Cancer Stem Cell-Related Biomarkers as Prognostic Factors
    Ko CCH, Chia WK, Selvarajah GT, Cheah YK, Wong YP, Tan GC
    Diagnostics (Basel), 2020 Sep 19;10(9).
    PMID: 32961774 DOI: 10.3390/diagnostics10090721
    Breast cancer is one of the leading causes of cancer-related deaths in women worldwide, and its incidence is on the rise. A small fraction of cancer stem cells was identified within the tumour bulk, which are regarded as cancer-initiating cells, possess self-renewal and propagation potential, and a key driver for tumour heterogeneity and disease progression. Cancer heterogeneity reduces the overall efficacy of chemotherapy and contributes to treatment failure and relapse. The cell-surface and subcellular biomarkers related to breast cancer stem cell (BCSC) phenotypes are increasingly being recognised. These biomarkers are useful for the isolation of BCSCs and can serve as potential therapeutic targets and prognostic tools to monitor treatment responses. Recently, the role of noncoding microRNAs (miRNAs) has extensively been explored as novel biomarker molecules for breast cancer diagnosis and prognosis with high specificity and sensitivity. An in-depth understanding of the biological roles of miRNA in breast carcinogenesis provides insights into the pathways of cancer development and its utility for disease prognostication. This review gives an overview of stem cells, highlights the biomarkers expressed in BCSCs and describes their potential role as prognostic indicators.
  13. Amycolatopsis nigrescens sp. nov., an actinomycete isolated from a Roman catacomb
    Groth I, Tan GYA, González JM, Laiz L, Carlsohn MR, Schütze B, et al.
    Int J Syst Evol Microbiol, 2007 Mar;57(Pt 3):513-519.
    PMID: 17329776 DOI: 10.1099/ijs.0.64602-0
    The taxonomic status of two actinomycetes isolated from the wall of a hypogean Roman catacomb was established based on a polyphasic investigation. The organisms were found to have chemical and morphological markers typical of members of the genus Amycolatopsis. They also shared a range of chemical, molecular and phenotypic markers which served to separate them from representatives of recognized Amycolatopsis species. The new isolates formed a branch in the Amycolatopsis 16S rRNA gene sequence tree with Amycolatopsis minnesotensis NRRL B-24435(T), but this association was not supported by a particularly high bootstrap value or by the product of the maximum-parsimony tree-making algorithm. The organisms were distinguished readily from closely related Amycolatopsis species based on a combination of phenotypic properties and from all Amycolatopsis strains by their characteristic menaquinone profiles, in which tetra-hydrogenated menaquinones with 11 isoprene units predominated. The combined genotypic and phenotypic data indicate that the isolates merit recognition as representing a novel species of the genus Amycolatopsis. The name proposed for this novel species is Amycolatopsis nigrescens sp. nov., with type strain CSC17Ta-90(T) (=HKI 0330(T)=DSM 44992(T)=NRRL B-24473(T)).
  14. Fulltext Prevalence of Ectoparasitism on Small Ruminants in Kelantan, Malaysia
    Syamsul VS, Okene IA, Yahya SNC, Hamdan RH, Lee SH, Tan LP
    Trop Life Sci Res, 2020 Apr;31(1):45-56.
    PMID: 32963710 DOI: 10.21315/tlsr2020.31.1.3
    Kelantan is a chiefly agrarian state with abundant small-holder ruminant farms in the East Coast economic Region of Malaysia. Ectoparasitism affects small ruminant production in Malaysia. It often causes reduction in meat quality and milk production which affect the farmers' income. To date, no report for the prevalence of ectoparasitism on small ruminant in Kelantan compared to other state in Malaysia. This study aims to determine the prevalence and associated risk factor of ruminant ectoparasitism in Kelantan. Ectoparasites were collected by manual picking and skin scrapping from 462 sheep and goats in Kelantan between April and September 2017 (during dry season). 60% of the sampled animals were infested with at least one species of the ectoparasites. In this study, lice and ticks were the most prevalent ectoparasites on small ruminant, which were 43.64% and 22.98%, respectively. The high biotic potential of lice population on host might be one of the factors they become the most prevalent species found on the animals. There was no significant relationship between ectoparasitism prevalence and species of small ruminants (χ2 = 1.12, p = 0.293). However, there was significant variations in prevalence between the regions where the animals were sampled from (χ2 = 30.25, p = 0.002) and farm management system for both species. This present study provides baseline epidemiological data on the prevalence of ectoparasitism in small ruminant. This information is useful for the formulation of prevention and control measures in order to enhance ruminant productivity in Kelantan.
  15. Fulltext The disruptive mobile wallet in the hospitality industry: An extended mobile technology acceptance model
    Lew S, Tan GW, Loh XM, Hew JJ, Ooi KB
    Technol Soc, 2020 Nov;63:101430.
    PMID: 33071395 DOI: 10.1016/j.techsoc.2020.101430
    Given that the mobile wallet has become a disruptive innovation, especially in the Malaysian hospitality industry, this study investigates the adoption of mobile wallet in the hospitality industry among consumers. Different from the extant literature, this study extends the newly proposed mobile technology acceptance model with self-efficacy theory, critical mass theory, and flow theory to explain the behavioural intention to adopt. A self-administered questionnaire was utilised to collect data from mobile wallet users who have used a mobile wallet while dining out in restaurants and cafes. Other than technology self-efficacy and perceived critical mass, mobile usefulness, mobile ease of use, mobile self-efficacy, and perceived enjoyment were discovered to have a positive and significant association with the behavioural intention to adopt mobile wallet in the hospitality industry. The findings also suggested there were interrelationships between the constructs employed. Overall, the extended model was able to explain 61% of the variance in behavioural intention to adopt mobile wallet.
  16. Fulltext Targeted delivery of 5-fluorouracil-1-acetic acid (5-FA) to cancer cells overexpressing epithelial growth factor receptor (EGFR) using virus-like nanoparticles
    Gan BK, Rullah K, Yong CY, Ho KL, Omar AR, Alitheen NB, et al.
    Sci Rep, 2020 Oct 08;10(1):16867.
    PMID: 33033330 DOI: 10.1038/s41598-020-73967-4
    Chemotherapy is widely used in cancer treatments. However, non-specific distribution of chemotherapeutic agents to healthy tissues and normal cells in the human body always leads to adverse side effects and disappointing therapeutic outcomes. Therefore, the main aim of this study was to develop a targeted drug delivery system based on the hepatitis B virus-like nanoparticle (VLNP) for specific delivery of 5-fluorouracil-1-acetic acid (5-FA) to cancer cells expressing epithelial growth factor receptor (EGFR). 5-FA was synthesized from 5-fluorouracil (5-FU), and it was found to be less toxic than the latter in cancer cells expressing different levels of EGFR. The cytotoxicity of 5-FA increased significantly after being conjugated on the VLNP. A cell penetrating peptide (CPP) of EGFR was displayed on the VLNP via the nanoglue concept, for targeted delivery of 5-FA to A431, HT29 and HeLa cells. The results showed that the VLNP displaying the CPP and harboring 5-FA internalized the cancer cells and killed them in an EGFR-dependent manner. This study demonstrated that the VLNP can be used to deliver chemically modified 5-FU derivatives to cancer cells overexpressing EGFR, expanding the applications of the VLNP in targeted delivery of chemotherapeutic agents to cancer cells overexpressing this transmembrane receptor.
  17. Neutron-activated theranostic radionuclides for nuclear medicine
    Tan HY, Yeong CH, Wong YH, McKenzie M, Kasbollah A, Md Shah MN, et al.
    Nucl Med Biol, 2020;90-91:55-68.
    PMID: 33039974 DOI: 10.1016/j.nucmedbio.2020.09.005
    Theranostics in nuclear medicine refers to personalized patient management that involves targeted therapy and diagnostic imaging using a single or combination of radionuclide (s). The radionuclides emit both alpha (α) or beta (β-) particles and gamma (γ) rays which possess therapeutic and diagnostic capabilities, respectively. However, the production of these radionuclides often faces difficulties due to high cost, complexity of preparation methods and that the products are often sourced far from the healthcare facilities, hence losing activity due to radioactive decay during transportation. Subject to the availability of a nuclear reactor within an accessible distance from healthcare facilities, neutron activation is the most practical and cost-effective route to produce radionuclides suitable for theranostic purposes. Holmium-166 (166Ho), Lutetium-177 (177Lu), Rhenium-186 (186Re), Rhenium-188 (188Re) and Samarium-153 (153Sm) are some of the most promising neutron-activated radionuclides that are currently in clinical practice and undergoing clinical research for theranostic applications. The aim of this paper is to review the physical characteristics, current clinical applications and future prospects of these neutron activated radionuclides in theranostics. The production, physical properties, validated clinical applications and clinical studies for each neutron-activated radionuclide suitable for theranostic use in nuclear medicine are reviewed in this paper.
  18. CYP3A5 genetic variants and their associations with carbamazepine and valproic acid response in Malaysian epileptic patients
    Miyata-Nozaka Y, Tan HJ, Wong SW, Raymond AA, Omar H, Zain SM
    Int J Clin Pharmacol Ther, 2021 Jan;59(1):8-16.
    PMID: 33026315 DOI: 10.5414/CP203761
    OBJECTIVE: Epilepsy is a common chronic neurological condition characterized by recurrent seizures. Approximately 30 - 40% of epileptic patients do not respond to antiepileptic drugs. Previous studies suggest that CYP3A5 polymorphisms affect carbamazepine metabolism.

    MATERIALS AND METHODS: To examine this hypothesis, in the present study, the associations between CYP3A5 variants (rs776746 and rs1419745) and response to carbamazepine and valproic acid monotherapy in Malaysian epileptic patients were evaluated.

    RESULTS: A total of 288 Malaysian epileptic patients were recruited and further reviewed, of whom 63 patients were on carbamazepine monotherapy, and 85 patients were on valproic acid monotherapy. There was no patient with drug hypersensitivity syndrome within the population. Subjects were genotyped by using Sequenom MassARRAY platform. This study found a significant association of CYP3A5 rs776746 with the carbamazepine treatment response in total patients (p = 0.026) and Malay ethnic subgroup (p = 0.006). In addition, a marginal significant association of CYP3A5 rs1419745 with carbamazepine treatment response was reported in the Malays. Similarly, CYP3A5 rs776746 was associated with valproic acid response in total patients (p = 0.037) and Malays (marginal p = 0.05).

    CONCLUSION: Our findings suggest that CYP3A5 polymorphisms affect carbamazepine and valproic acid response in Malaysian epileptic patients.

  19. Falls, frailty, and metabolic syndrome in urban dwellers aged 55 years and over in the Malaysian elders longitudinal research (MELoR) study - a cross-sectional Study
    Teoh RJJ, Mat S, Khor HM, Kamaruzzaman SB, Tan MP
    Postgrad Med, 2021 Apr;133(3):351-356.
    PMID: 33143493 DOI: 10.1080/00325481.2020.1842026
    OBJECTIVES: While metabolic syndrome, falls, and frailty are common health issues among older adults which are likely to be related, the potential interplay between these three conditions has not previously been investigated. We investigated the relationship between metabolic syndrome with falls, and the role of frailty markers in this potential relationship, among community-dwelling older adults.

    METHODS: Data from the first wave Malaysian Elders Longitudinal Research (MELoR) study comprising urban dwellers aged 55 years and above were utilized. Twelve-month fall histories were established during home-based, computer-assisted interviews which physical performance, anthropometric and laboratory measures were obtained during a hospital-based health check. Gait speed, exhaustion, weakness, and weight loss were employed as frailty markers.

    RESULTS: Data were available for 1415 participants, mean age of 68.56 ± 7.26 years, 57.2% women. Falls and metabolic syndrome were present in 22.8% and 44.2%, respectively. After adjusting for age, sex, and multiple comorbidities, metabolic syndrome was significantly associated with falls in the sample population [odds ratio (OR): 1.33, 95% confidence interval (CI): 1.03; 1.72]. This relationship was attenuated by the presence of slow gait speed, but not exhaustion, weakness, or weight loss.

    CONCLUSION: Metabolic syndrome was independently associated with falls among older adults, and this relationship was accounted for by the presence of slow gait speed. Future studies should determine the value of screening for frailty and falls with gait speed in older adults with metabolic syndrome as a potential fall prevention measure.

  20. Adult Endogenous Dopaminergic Neuroregeneration Against Parkinson's Disease: Ideal Animal Models?
    Vijayanathan Y, Lim SM, Tan MP, Lim FT, Majeed ABA, Ramasamy K
    Neurotox Res, 2021 Apr;39(2):504-532.
    PMID: 33141428 DOI: 10.1007/s12640-020-00298-7
    Parkinson's disease (PD) is the second most common neurodegenerative disease. The etiology of PD remains an enigma with no available disease modifying treatment or cure. Pharmacological compensation is the only quality of life improving treatments available. Endogenous dopaminergic neuroregeneration has recently been considered a plausible therapeutic strategy for PD. However, researchers have to first decipher the complexity of adult endogenous neuroregeneration. This raises the need of animal models to understand the underlying molecular basis. Mammalian models with highly conserved genetic homology might aid researchers to identify specific molecular mechanisms. However, the scarcity of adult neuroregeneration potential in mammals obfuscates such investigations. Nowadays, non-mammalian models are gaining popularity due to their explicit ability to neuroregenerate naturally without the need of external enhancements, yet these non-mammals have a much diverse gene homology that critical molecular signals might not be conserved across species. The present review highlights the advantages and disadvantages of both mammalian and non-mammalian animal models that can be essentially used to study the potential of endogenous DpN regeneration against PD.
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