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  1. Lim, Wai Feng, Muniandi, Logeswaran, George, Elizabeth, Sathar, Jameela, Teh, Lai Kuan, Lai, Mei I.
    MyJurnal
    HbE/β-thalassaemia is a compound heterozygous mutation with a vast clinical phenotype [1]. To improve quality of life, HbE/β-thalassaemia individuals receive different treatment strategies, either individually or in combination with therapy(ies), including blood transfusion, iron chelation and splenectomy [2-3]. Thus far, there are limited studies conducted regarding the effect of treatments in HbE/β-thalassaemia individuals. We hereby investigated the effect of treatments with respect to red blood cell indices, haemoglobin subtypes and gene expressions among 30 HbE/beta-thalassaemia individuals. Statistical analyses were carried out using SPSS 17.0. As compared to single therapy (transfused only individuals) and double therapies (transfused-chelated only individuals), individuals receiving triple therapies (transfused-chelated-splenectomised individuals) showed significantly high mean cell volume (MCV), mean cell haemoglobin (MCH) and reticulocytes count (Fig.1).

    These findings suggest that triple therapies are the most effective in ameliorating the severity of the disease in terms of microcytosis and hypochromia [3-5]. The high reticulocyte count in triple therapies also allows the bone marrow to actively produce red blood cells suggesting that these therapies have clinical benefits by suppressing the ineffective erythropoiesis and improving the erythropoietic environment significantly among HbE/β-thalassaemia individuals in our studied group [6-7].

    The effectiveness of these treatments is different among each HbE/β-thalassaemia individual whereby clinical variabilities among them could be a contributing factor. Triple therapies giving the best advantage to the HbE/β-thalassaemia patient in this study.
  2. Lim WF, Mohamad Yusof MI, Teh LK, Salleh MZ
    Nutrients, 2020 Sep 30;12(10).
    PMID: 33007803 DOI: 10.3390/nu12102993
    Moringa oleifera is a miracle plant with many nutritional and medicinal properties. Chemopreventive values of the combined mixture of moringa leaves and seed residue (MOLSr) at different ratios (M1S9, M1S1 and M9S1) were investigated. MOLSr extracts were subjected to phytochemical screening, antioxidant assays, metabolite profiling and cytotoxic activity on the primary mammary epithelial cells (PMECs), non-malignant Chang's liver cells and various human cancer cell lines (including breast, cervical, colon and liver cancer cell lines). The MOLSr ratio with the most potent cytotoxic activity was used in xenograft mice injected with MDA-MB-231 cells for in vivo tumorigenicity study as well as further protein and gene expression studies. M1S9, specifically composed of saponin and amino acid, retained the lowest antioxidant activity but the highest glucosinolate content as compared to other ratios. Cell viability decreased significantly in MCF-7 breast cancer cells and PMECs after treatment with M1S9. Solid tumor from MDA-MB-231 xenograft mice was inhibited by up to 64.5% at third week after treatment with high-dose M1S9. High-dose M1S9 significantly decreased the expression of calcineurin (CaN) and vascular endothelial cell growth factor (VEGF) proteins as well as the secreted frizzled-related protein 1 (SFRP1) and solute carrier family 39 member 6 (SLC39A6) genes. This study provides new scientific evidence for the chemoprevention potential of MOLSr extracts in a breast cancer model; however, the precise mechanism warrants further investigation.
  3. Kang CC, Lee TY, Lim WF, Yeo WWY
    Clin Transl Sci, 2023 Nov;16(11):2078-2094.
    PMID: 37702288 DOI: 10.1111/cts.13640
    Moving away from traditional "one-size-fits-all" treatment to precision-based medicine has tremendously improved disease prognosis, accuracy of diagnosis, disease progression prediction, and targeted-treatment. The current cutting-edge of 5G network technology is enabling a growing trend in precision medicine to extend its utility and value to the smart healthcare system. The 5G network technology will bring together big data, artificial intelligence, and machine learning to provide essential levels of connectivity to enable a new health ecosystem toward precision medicine. In the 5G-enabled health ecosystem, its applications involve predictive and preventative measurements which enable advances in patient personalization. This review aims to discuss the opportunities, challenges, and prospects posed to 5G network technology in moving forward to deliver personalized treatments and patient-centric care via a precision medicine approach.
  4. Lim WF, Muniandi L, George E, Sathar J, Teh LK, Gan GG, et al.
    Blood Cells Mol. Dis., 2012 Jan 15;48(1):17-21.
    PMID: 22079025 DOI: 10.1016/j.bcmd.2011.10.002
    The alpha haemoglobin stabilising protein (AHSP) acts as a molecular chaperone for α-globin by stabilising nascent α-globin before transferring it to waiting free β-globin chains. Binding of AHSP to α-globin renders α-globin chemically inert whereby preventing it from precipitating and forming reactive oxygen species byproducts. The AHSP has been actively studied in the recent years, particularly in its relation to β-thalassaemia. Studies have shown that AHSP is a modifier in β-thalassaemia mice models. However, this relationship is less established in humans. Studies by some groups showed no correlation between the AHSP haplotypes and the severity of β-thalassaemia, whereas others have shown that certain AHSP haplotype could modify the phenotype of β-thalassaemia intermedia patients. We investigated the expression of AHSP in relation to selected demographic data, full blood count, HPLC results, HbE/β-thalassaemia genotype, Xmn-1 Gγ polymorphism, α-globin, β-globin and γ-globin expression. We found that AHSP expression was significantly correlated to mean cell haemoglobin level, HbF %, α-globin, β-globin and excess α-globin expression. We concluded that AHSP could be a secondary compensatory mechanism in red blood cells to counterbalance the excess α-globin chains in HbE/β-thalassaemia individuals.
  5. Lim WF, Nasir SM, Teh LK, James RJ, Izhar MHM, Salleh MZ
    Turk J Biol, 2020;44(6):437-448.
    PMID: 33402870 DOI: 10.3906/biy-2005-2
    Garcinia species are widely used for their slimming effects via increased fat burning and suppression of satiety. However, scientific evidence for the biological effects of Garcinia atroviridis (GA) is lacking. We investigated the phytochemical composition, safety profiles, and antioxidant and antiobesity effects of methanolic extracts of Garcinia atroviridis (MeGa) in obese female rats. Repeated dose toxicity studies were conducted according to the OECD guidelines. Upon sacrifice, haematological, biochemical, lipid profile, and serum-based metabolomics analyses were performed to evaluate metabolic expression changes and their related pathways. MeGa contains several phytochemical groups and GA fruit acids. MeGa was found to be nontoxic in both male and female rats with an oral lethal dose (LD50) of 2000 mg/kg. After 9 weeks of treatment, MeGa-treated obese rats had lower weight gain and better lipid profiles (cholesterol and triglyceride), which correlated with the altered metabolic pathways involved in the metabolism of lipid (glycerophospholipid) and biosynthesis of unsaturated fatty acid. In addition, MeGa caused differential metabolism pathways of arachidonic acid and tryptophan that affect the inflammatory response and suppression of appetite. We concluded that MeGa is safe, and its slimming effects are due to the differential metabolism of lipids.
  6. Yap BK, M Soair SN, Talik NA, Lim WF, Mei I L
    Sensors (Basel), 2018 Aug 10;18(8).
    PMID: 30103424 DOI: 10.3390/s18082625
    Over the past 20 years, rapid technological advancement in the field of microfluidics has produced a wide array of microfluidic point-of-care (POC) diagnostic devices for the healthcare industry. However, potential microfluidic applications in the field of nutrition, specifically to diagnose iron deficiency anemia (IDA) detection, remain scarce. Iron deficiency anemia is the most common form of anemia, which affects billions of people globally, especially the elderly, women, and children. This review comprehensively analyzes the current diagnosis technologies that address anemia-related IDA-POC microfluidic devices in the future. This review briefly highlights various microfluidics devices that have the potential to detect IDA and discusses some commercially available devices for blood plasma separation mechanisms. Reagent deposition and integration into microfluidic devices are also explored. Finally, we discuss the challenges of insights into potential portable microfluidic systems, especially for remote IDA detection.
  7. Lee TY, Farah N, Chin VK, Lim CW, Chong PP, Basir R, et al.
    Nutr Res, 2023 Nov;119:1-20.
    PMID: 37708600 DOI: 10.1016/j.nutres.2023.08.010
    Riboflavin is a precursor of the essential coenzymes flavin mononucleotide and flavin adenine dinucleotide. Both possess antioxidant properties and are involved in oxidation-reduction reactions, which have a significant impact on energy metabolism. Also, the coenzymes participate in metabolism of pyridoxine, niacin, folate, and iron. Humans must obtain riboflavin through their daily diet because of the lack of programmed enzymatic machineries for de novo riboflavin synthesis. Because of its physiological nature and fast elimination from the human body when in excess, riboflavin consumed is unlikely to induce any negative effects or develop toxicity in humans. The use of riboflavin in pharmaceutical and clinical contexts has been previously explored, including for preventing and treating oxidative stress and reperfusion oxidative damage, creating synergistic compounds to mitigate colorectal cancer, modulating blood pressure, improving diabetes mellitus comorbidities, as well as neuroprotective agents and potent photosensitizer in killing bloodborne pathogens. Thus, the goal of this review is to provide a comprehensive understanding of riboflavin's biological applications in medicine, key considerations of riboflavin safety and toxicity, and a brief overview on the nanoencapsulation of riboflavin for various functions including the treatment of a range of diseases, photodynamic therapy, and cellular imaging.
  8. Fauzi MF, Anuar TS, Teh LK, Lim WF, James RJ, Ahmad R, et al.
    PMID: 33809939 DOI: 10.3390/ijerph18063269
    Stress, anxiety, and depression (SAD) have a negative impact on the learning and academic performance of university students. Hence, this study aimed to determine the prevalence, as well as the risk factors associated with SAD among a cohort of students pursuing undergraduate degree courses in health sciences. This is part of the strategy in building a healthy nation. A questionnaire containing socio-demographic factors and the short version of Depression, Anxiety, and Stress Scale-21 (DASS-21) was used to assess the likelihood of psychological distress. Logistic regression analysis was conducted to determine the risk factors of SAD. In total, 449 students completed the questionnaire (93.9% response rate). Of these, 65% had stress, 85.1% had anxiety and 51.4% had depression. Most cases of stress (74.6%) and depression (66.2%) were of normal-to-mild level, while 74.6% of them showed moderate-to-extremely severe anxiety. There was a statistically significant association between stress score and the year of study. In the regression analysis, poor sleep quality and fatigue were risk factors of anxiety and depression, whereas low-grade fever and frequent headaches were risk factors for stress and anxiety. Stress, anxiety, and depression scores were significantly higher among students studying medical imaging. A substantial proportion of health science students are suffering from SAD. This study recommends screening and close monitoring of the above-mentioned predictors and the formulation of comprehensive intervention strategies for students with SAD.
  9. Zainal Abidin N, Noorizhab MNF, Teh LK, Lim WF, Mohd Noordin N, Aziz ZA, et al.
    Microbiol Resour Announc, 2021 Jun 24;10(25):e0035221.
    PMID: 34165334 DOI: 10.1128/MRA.00352-21
    In the battle against tuberculosis (TB), plasticity of the Mycobacterium tuberculosis genome is believed to contribute to the pathogen's virulence and drug resistance. Here, we report 10 draft genome sequences of clinical M. tuberculosis isolated in Malaysia as the basis for understanding the genome plasticity of the M. tuberculosis isolates.
  10. Noorizhab Fakhruzzaman MN, Abidin NZ, Aziz ZA, Lim WF, Richard JJ, Noorliza MN, et al.
    Int J Mycobacteriol, 2019 12 4;8(4):320-328.
    PMID: 31793500 DOI: 10.4103/ijmy.ijmy_144_19
    Background: Tuberculosis (TB) is still a major health problem in Malaysia with thousands of cases reported yearly. This is further burdened with the emergence of multidrug-resistant TB (MDR-TB). Whole-genome sequencing (WGS) provides high-resolution molecular epidemiological data for the accurate determination of Mycobacterium tuberculosis complex (MTBC) lineages and prediction of the drug-resistance patterns. This study aimed to investigate the diversity of MTBC in Malaysia in terms of lineage and drug-resistance patterns of the clinical MTBC isolates using WGS approach.

    Methods: The genomes of 24 MTBC isolated from sputum and pus samples were sequenced. The phenotypic drug susceptibility testing (DST) of the isolates was determined for ten anti-TB drugs. Bioinformatic analysis comprising genome assembly and annotation and single-nucleotide polymorphism (SNP) analysis in genes associated with resistance to the ten anti-TB drugs were done on each sequenced genome.

    Results: The draft assemblies covered an average of 97% of the expected genome size. Eleven isolates were aligned to the Indo-Oceanic lineage, eight were East-Asian lineage, three were East African-Indian lineage, and one was of Euro-American and Bovis lineages, respectively. Twelve of the 24 MTBC isolates were phenotypically MDR M. tuberculosis: one is polyresistance and another one is monoresistance. Twenty-six SNPs across nine genes associated with resistance toward ten anti-TB drugs were detected where some of the mutations were found in isolates that were previously reported as pan-susceptible using DST. A haplotype consisting of 65 variants was also found among the MTBC isolates with drug-resistance traits.

    Conclusions: This study is the first effort done in Malaysia to utilize 24 genomes of the local clinical MTBC isolates. The high-resolution molecular epidemiological data obtained provide valuable insights into the mechanistic and epidemiological qualities of TB within the vicinity of Southeast Asia.

  11. Azami NAM, Perera D, Thayan R, AbuBakar S, Sam IC, Salleh MZ, et al.
    Int J Infect Dis, 2022 Dec;125:216-226.
    PMID: 36336246 DOI: 10.1016/j.ijid.2022.10.044
    OBJECTIVES: This study reported SARS-CoV-2 whole genome sequencing results from June 2021 to January 2022 from seven genome sequencing centers in Malaysia as part of the national surveillance program.

    METHODS: COVID-19 samples that tested positive by reverse transcription polymerase chain reaction and with cycle threshold values <30 were obtained throughout Malaysia. Sequencing of SARS-CoV-2 complete genomes was performed using Illumina, Oxford Nanopore, or Ion Torrent platforms. A total of 6163 SARS-CoV-2 complete genome sequences were generated over the surveillance period. All sequences were submitted to the Global Initiative on Sharing All Influenza Data database.

    RESULTS: From June 2021 to January 2022, Malaysia experienced the fourth wave of COVID-19 dominated by the Delta variant of concern, including the original B.1.617.2 lineage and descendant AY lineages. The B.1.617.2 lineage was identified as the early dominant circulating strain throughout the country but over time, was displaced by AY.59 and AY.79 lineages in Peninsular (west) Malaysia, and the AY.23 lineage in east Malaysia. In December 2021, pilgrims returning from Saudi Arabia facilitated the introduction and spread of the BA.1 lineage (Omicron variant of concern) in the country.

    CONCLUSION: The changing trends of circulating SARS-CoV-2 lineages were identified, with differences observed between west and east Malaysia. This initiative highlighted the importance of leveraging research expertise in the country to facilitate pandemic response and preparedness.

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