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  1. Fulltext Effect of transfusion, iron chelation and splenectomy therapies in HbE/β-thalassaemia individuals in Malaysia
    Lim, Wai Feng, Muniandi, Logeswaran, George, Elizabeth, Sathar, Jameela, Teh, Lai Kuan, Lai, Mei I.
    Journal of Biomedical and Clinical Sciences, 2017;2(202):60-61.
    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. Fulltext Effects of Sonication and Thermal Pasteurization on the Nutritional, Antioxidant, and Microbial Properties of Noni Juice
    Choo YX, Teh LK, Tan CX
    Molecules, 2022 Dec 30;28(1).
    PMID: 36615507 DOI: 10.3390/molecules28010313
    Sonication is recognized as a potential food processing method to improve the functional properties of fruit juice. This study evaluated the effects of different sonication durations (20, 40, and 60 min) and thermal pasteurization on the nutritional, antioxidant, and microbial properties of noni juice. Fresh noni juice served as the control. The main organic acids detected were malic (57.54−89.31 mg/100 mL) and ascorbic (17.15−31.55 mg/100 mL) acids. Compared with the fresh sample, the concentrations of these compounds were significantly improved (p < 0.05) in the 60 min sonicated sample but reduced (p < 0.05) in the pasteurized sample. Moreover, sonication for 60 min resulted in increments of scopoletin, rutin, and vanillic acid compared to the fresh sample. The antioxidant activity of the juice sample was improved in the sample sonicated for 60 min. Irrespective of juice processing method, the level of microbial counts in noni juice was within the satisfactory level over the 8 weeks of refrigerated (4 °C) storage. This study highlights the feasibility of using ultrasound processing to enhance the quality of noni juice on the industrial scale.
  3. HbA2 levels in β-thalassaemia carriers with the Filipino β0-deletion: are the levels higher than what is found with non-deletional forms of β0-thalassaemia?
    George E, Teh LK, Tan J, Lai MI, Wong L
    Pathology, 2013 01;45(1):62-5.
    PMID: 23222244 DOI: 10.1097/PAT.0b013e32835af7c1
    AIMS: Classical carriers of β-thalassaemia are identified by a raised HbA2 level. Earlier studies indicated that the Filipino β-deletion has high raised HbA2 levels. The introduction of automated high performance liquid chromatography (HPLC) for thalassaemia screening is an important advance in technology for haematology laboratories. The BioRad Variant II Hb analyser is a common instrument used to quantify HbA2 levels in thalassaemia screening. This study aimed to determine HbA2 levels in carriers of Filipino β-mutation using the BioRad Variant II Hb analyser.

    METHODS: The Filipino β-deletion was identified using gap-polymerase chain reaction (PCR) in the parents of transfusion dependent β-thalassaemia patients who were homozygous for the Filipino β-deletion in the indigenous population of Sabah, Malaysia. Hb subtypes were quantified on the BioRad Variant II Hb analyser. Concurrent α-thalassaemia was identified by multiplex gap-PCR for deletions and amplification refractory mutation system (ARMS)-PCR for non-deletional mutations.

    RESULTS: The mean HbA2 level for Filipino β-thalassaemia trait was 5.9 ± 0.47 and with coinheritance of α-thalassaemia was 6.3 ± 0.44 (-α heterozygous) and 6.7 ± 0.36 (-α homozygous). The HbA2 levels were all >4% in keeping with the findings of classical β-thalassaemia trait and significantly higher than levels seen in non-deletional forms of β-thalassaemia.

    CONCLUSION: The HbA2 level measured on the BioRad Variant II Hb analyser was lower than the level in the first description of the Filipino β-thalassaemia. β-thalassaemia trait with coinheritance of α-thalassaemia (-α) is associated with significantly higher HbA2 level.

  4. Recent Advances in the Genetics of Hypertension
    Wei LK, Au A, Teh LK, Lye HS
    Adv Exp Med Biol, 2017;956:561-581.
    PMID: 27957710 DOI: 10.1007/5584_2016_75
    Hypertension is a silent killer worldwide, caused by both genetic and environmental factors. Until now, genetic and genomic association studies of hypertension are reporting different degree of association on hypertension. Hence, it is essential to gather all the available information on the reported genetic loci and to determine if any biomarker(s) is/are significantly associated with hypertension. Current review concluded the potential biomarkers for hypertension, with regards to electrolyte and fluid transports, as well as sodium/potassium ions homeostasis, which are supported by the results of case-controls and meta-analyses.
  5. Molecular basis of transfusion dependent beta-thalassemia major patients in Sabah
    Teh LK, George E, Lai MI, Tan JA, Wong L, Ismail P
    J Hum Genet, 2014 Mar;59(3):119-23.
    PMID: 24369358 DOI: 10.1038/jhg.2013.131
    Beta-thalassemia is one of the most prevalent inherited diseases and a public health problem in Malaysia. Malaysia is geographically divided into West and East Malaysia. In Sabah, a state in East Malaysia, there are over 1000 estimated cases of β-thalassemia major patients. Accurate population frequency data of the molecular basis of β-thalassemia major are needed for planning its control in the high-risk population of Sabah. Characterization of β-globin gene defects was done in 252 transfusion dependent β-thalassemia patients incorporating few PCR techniques. The study demonstrates that β-thalassemia mutations inherited are ethnically dependent. It is important to note that 86.9% of transfusion-dependent β-thalassemia major patients in Sabah were of the indigenous population and homozygous for a single mutation. The Filipino β(0)-deletion was a unique mutation found in the indigenous population of Sabah. Mutations common in West Malaysia were found in 11 (4.3%) patients. Four rare mutations (Hb Monroe, CD 8/9, CD 123/124/125 and IVS I-2) were also found. This study is informative on the population genetics of β-thalassemia major in Sabah.
  6. α-Haemoglobin stabilising protein expression is influenced by mean cell haemoglobin and HbF levels in HbE/β-thalassaemia individuals
    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.
  7. Fulltext Correlation of BACH1 and Hemoglobin E/Beta-Thalassemia Globin Expression
    Lee TY, Muniandy L, Teh LK, Abdullah M, George E, Sathar J, et al.
    Turk J Haematol, 2016 Mar 05;33(1):15-20.
    PMID: 26377036 DOI: 10.4274/tjh.2014.0197
    The diverse clinical phenotype of hemoglobin E (HbE)/β-thalassemia has not only confounded clinicians in matters of patient management but has also led scientists to investigate the complex mechanisms involved in maintaining the delicate red cell environment where, even with apparent similarities of α- and β-globin genotypes, the phenotype tells a different story. The BTB and CNC homology 1 (BACH1) protein is known to regulate α- and β-globin gene transcriptions during the terminal differentiation of erythroid cells. With the mutations involved in HbE/β-thalassemia disorder, we studied the role of BACH1 in compensating for the globin chain imbalance, albeit for fine-tuning purposes.
  8. Lipid Metabolism Genes in Stroke Pathogenesis: The Atherosclerosis
    Chow YL, Teh LK, Chyi LH, Lim LF, Yee CC, Wei LK
    Curr Pharm Des, 2020;26(34):4261-4271.
    PMID: 32534558 DOI: 10.2174/1381612826666200614180958
    Stroke is the second leading cause of death and a major cause of disability worldwide. Both modifiable and non-modifiable risk factors can affect the occurrence of ischemic stroke at varying degrees. Among them, atherosclerosis has been well-recognized as one of the main culprits for the rising incidence of stroke-related mortality. Hence, the current review aimed to summarize the prominent role of lipid metabolism genes such as PCSK9, ApoB, ApoA5, ApoC3, ApoE, and ABCA1 in mediating ischemic stroke occurrence.
  9. Identification and characterization of antioxidant peptides from hydrolysate of blue-spotted stingray and their stability against thermal, pH and simulated gastrointestinal digestion treatments
    Wong FC, Xiao J, Ong MG, Pang MJ, Wong SJ, Teh LK, et al.
    Food Chem, 2019 Jan 15;271:614-622.
    PMID: 30236723 DOI: 10.1016/j.foodchem.2018.07.206
    This study was conducted to identify and characterize antioxidant peptides from the alcalase hydrolysate of the blue-spotted stingray. Purification steps guided by ABTS cation radical (ABTS+) scavenging assay and de novo peptide sequencing produced two peptides, WAFAPA (661.3224 Da) and MYPGLA (650.3098 Da). WAFAPA (EC50 = 12.6 µM) had stronger antioxidant activity than glutathione (EC50 = 13.7 µM) and MYPGLA (EC50 = 19.8 µM). Synergism between WAFAPA and MYPGLA was detected. WAFAPA and MYPGLA surpassed carnosine in their ability to suppress H2O2-induced lipid oxidation. The peptides protected plasmid DNA and proteins from Fenton's reagent-induced oxidative damage. Thermal (25-100 °C) and pH 3-11 treatments did not alter antioxidant activity of the peptides. MYPGLA maintained its antioxidant activity after simulated gastrointestinal digestion, whereas WAFAPA showed a partial loss. The two peptides may have potential applications as functional food ingredients or nutraceuticals, whether used singly or in combination.
  10. Modifying progression of aging and reducing the risk of neurodegenerative diseases by probiotics and synbiotics
    Lye HS, Lee YT, Ooi SY, Teh LK, Lim LN, Wei LK
    Front Biosci (Elite Ed), 2018 03 01;10:344-351.
    PMID: 29293462
    Aging, which affects most of the multi-cellular organisms, is due to a potentially complex set of mechanisms that collectively cause a time-dependent decline of physiological functions. Aging restrains longevity and leads to neurodegenerative diseases including dementia, Alzheimer's disease and lacunar stroke. Human microbiota is now considered to have a strong impact on the progression of aging. The impact of aging and the risk of neurodegenerative diseases can be reduced by using probiotics, or preferably by combining probiotics and prebiotics, also known as synbiotics, that can drastically modify the composition of gut microbiome.
  11. Fulltext Screening for intermediate and severe forms of thalassaemia in discarded red blood cells: optimization and feasibility
    George E, Lai MI, Teh LK, Ramasamy R, Goh EH, Asokan K, et al.
    Med J Malaysia, 2011 Dec;66(5):429-34.
    PMID: 22390095 MyJurnal
    Detection and quantification of Hb subtypes of human blood is integral to presumptive identification of thalassaemias. It has been used in neonatal screening of thalassaemia and Hb variants. The use of discarded red blood cells following processing of the cord blood for stem cells provides readily available diagnostic material for thalassaemia screening. In this study, we determined the range of Hb subtypes in 195 consecutive cord blood samples collected for cord blood banking. The 'cord blood samples' analysed were those of the remaining red blood cells after the cord blood was processed for stem cell storage. Quantification of Hb subtypes by high performance liquid chromatography (HPLC) was done on BioRad Variant II Hb testing system. Only 73 (36.5%) of the samples could be analyzed neat without dilution. With a 1:300 dilution with wash solution the acceptable area as recommended by the manufacturer for reading of a C-gram within the 1 to 3 million ranges were achieved in all. Eighteen (9%) 12 showed classical Hb Barts (y4) prerun peaks were confirmed by Sebia Hydrasys automated Hb gel electrophoresis and quantified by Sebia Capillarys 2 capillary electrophoresis. Only 1 (0.5%) was presumptively identified with HbH disease. Due to the limited number of samples no beta-thalassaemia major, Hb E beta-thalassaemia and Hb Barts hydrops fetalis were found. The HPLC assay was possible at a cost US$ 5 per sample and a turnover time of 10 samples per hour without technical difficulties. This study reports an effective and valuable protocol for thalassaemia screening in red blood cells which would otherwise be discarded during cord blood processing. Cord blood with severe and intermediate forms of thalassaemia can be preselected and not stored.
  12. Fulltext Purification and identification of novel cytotoxic oligopeptides from soft coral Sarcophyton glaucum
    Quah Y, Mohd Ismail NI, Ooi JLS, Affendi YA, Abd Manan F, Teh LK, et al.
    J Zhejiang Univ Sci B, 2019 1 8;20(1):59-70.
    PMID: 30614230 DOI: 10.1631/jzus.B1700586
    Globally, peptide-based anticancer therapies have drawn much attention. Marine organisms are a reservoir of anticancer peptides that await discovery. In this study, we aimed to identify cytotoxic oligopeptides from Sarcophyton glaucum. Peptides were purified from among the S. glaucum hydrolysates produced by alcalase, chymotrypsin, papain, and trypsin, guided by a methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay on the human cervical cancer (HeLa) cell line for cytotoxicity evaluation. Purification techniques adopted were membrane ultrafiltration, gel filtration chromatography, solid phase extraction (SPE), and reversed-phase high-performance liquid chromatography (RP-HPLC). Purified peptides were identified by de novo peptide sequencing. From papain hydrolysate, three peptide sequences were identified: AGAPGG, AERQ, and RDTQ (428.45, 502.53, and 518.53 Da, respectively). Peptides synthesized from these sequences exhibited cytotoxicity on HeLa cells with median effect concentration (EC50) values of 8.6, 4.9, and 5.6 mmol/L, respectively, up to 5.8-fold stronger than the anticancer drug 5-fluorouracil. When tested at their respective EC50, AGAPGG, AERQ, and RDTQ showed only 16%, 25%, and 11% cytotoxicity to non-cancerous Hek293 cells, respectively. In conclusion, AERQ, AGAPGG, and RDTQ are promising candidates for future development as peptide-based anticancer drugs.
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