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  1. Subramaniam S, Balasubramaniam V, Sinniah M, Thayan R, Lim LY
    Malays J Pathol, 1993 Dec;15(2):143-6.
    PMID: 8065176
    HIV-1 antibody patterns in two groups, those infected by the intravenous route (IV drug users) and those infected by the sexual route (prostitutes, male homosexuals and sexually transmitted disease patients) were compared using the Western blot technique. A total of 160 cases were studied. The intravenous drug user (IVDU) group appeared to respond to fewer antibody markers than the sexually infected group, the difference being significant for markers p31, p51, p55, p66, gp41 and gp120. Furthermore, a higher proportion (63%) of the sexually infected group carried antibodies to all Western blot markers as compared to the IVDU group (49%).
  2. Zulkurnain M, Balasubramaniam VM, Maleky F
    Molecules, 2019 Aug 06;24(15).
    PMID: 31390764 DOI: 10.3390/molecules24152853
    Different fractions of fully hydrogenated soybean oil (FHSBO) in soybean oil (10-30% w/w) and the addition of 1% salt (sodium chloride) were used to investigate the effect of high-pressure treatments (HP) on the crystallization behaviors and physical properties of the binary mixtures. Sample microstructure, solid fat content (SFC), thermal and rheological properties were analyzed and compared against a control sample (crystallized under atmospheric condition). The crystallization temperature (Ts) of all model fats under isobaric conditions increased quadratically with pressure until reaching a pressure threshold. As a result of this change, the sample induction time of crystallization (tc) shifted from a range of 2.74-0.82 min to 0.72-0.43 min when sample crystallized above the pressure threshold under adiabatic conditions. At the high solid mass fraction, the addition of salt reduced the pressure threshold to induce crystallization during adiabatic compression. An increase in pressure significantly reduced mean cluster diameter in relation to the reduction of tc regardless of the solid mass fraction. In contrast, the sample macrostructural properties (SFC, storage modulus) were influenced more significantly by solid mass fractions rather than pressure levels. The creation of lipid gel was observed in the HP samples at 10% FHSBO. The changes in crystallization behaviors indicated that high-pressure treatments were more likely to influence crystallization mechanisms at low solid mass fraction.
  3. Tan LY, Komarasamy TV, Rmt Balasubramaniam V
    Front Immunol, 2021;12:742941.
    PMID: 34659238 DOI: 10.3389/fimmu.2021.742941
    The coronavirus disease-19 (COVID-19) elicited by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused devastating health, economic and social impact worldwide. Its clinical spectrum ranges from asymptomatic to respiratory failure and multi-organ failure or death. The pathogenesis of SARS-CoV-2 infection is attributed to a complex interplay between virus and host immune response. It involves activation of multiple inflammatory pathways leading to hyperinflammation and cytokine storm, resulting in tissue damage, acute respiratory distress syndrome (ARDS) and multi-organ failure. Accumulating evidence has raised concern over the long-term health effects of COVID-19. Importantly, the neuroinvasive potential of SARS-CoV-2 may have devastating consequences in the brain. This review provides a conceptual framework on how the virus tricks the host immune system to induce infection and cause severe disease. We also explore the key differences between mild and severe COVID-19 and its short- and long-term effects, particularly on the human brain.
  4. Balasubramaniam V, Sinniah M, Tan DS, Redzwan G, Lo'man SG
    Med J Malaysia, 1994 Jun;49(2):113-6.
    PMID: 8090088
    A previous cross-sectional serological survey of various age groups (0-55 years) of the Malaysian normal population showed that cytomegalovirus (CMV) infection is highly endemic in Malaysia. A total of 1,688 infants (0-4 months) with congenital abnormalities were screened for evidence of congenital CMV infection and the rest of the TORCHES (TOxoplasmosis, Rubella, Cytomegalovirus, HErpes simplex, Syphilis) group of congenital infections. Congenital CMV infection was detected in 193 (11.4%) infants which is significantly higher than the prevalence of congenital syphilis (4%), congenital rubella infection (3.7%), congenital toxoplasma (1.0%) and congenital herpes simplex virus infection (0%). Of the 193 cases, 10.4 per cent had CNS defects. We concluded that 1) congenital CMV appears to be the most important cause of congenital infections among the TORCHES diseases in Malaysia; and 2) secondary rather than primary infections or reactivation is responsible for most of the intrauterine CMV infection in Malaysia, as primary infection is usually associated with neurological involvement.
  5. Balasubramaniam V, June Chelyn L, Vimala S, Mohd Fairulnizal MN, Brownlee IA, Amin I
    Heliyon, 2020 Aug;6(8):e04654.
    PMID: 32817893 DOI: 10.1016/j.heliyon.2020.e04654
    Three species of Malaysian edible seaweed (Eucheuma denticulatum, Sargassum polycystum and Caulerpa lentillifera) were analyzed for their carotenoid composition using a combination of high-performance thin layer chromatography (HPTLC) and ultra-high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UHPLC-ESI-MS/MS), while the antioxidant capacities were determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and oxygen radical absorbance capacity (ORAC) assays. The HPTLC analysis exhibited a distinct carotenoid pattern among the three seaweed groups. The UHPLC-ESI-MS/MS analysis showed fucoxanthin as the major carotenoid present in S. polycystum while lutein and zeaxanthin in E. denticulatum. For C. lentillifera, β-carotene and canthaxanthin were the major carotenoids. Some of the carotenoids, such as rubixanthin, dinoxanthin, diatoxanthin and antheraxanthin, were also tentatively detected in E. denticulatum and S. polycystum. For antioxidant activity, S. polycystum (20 %) and E. denticulatum (1128 μmol TE/g) showed the highest activity in the DPPH and ORAC assays, respectively. The findings suggest the three edible varieties of seaweeds may provide a good dietary source with a potential to reduce antioxidative stress.
  6. Tham HW, Balasubramaniam V, Ooi MK, Chew MF
    Front Microbiol, 2018;9:1040.
    PMID: 29875751 DOI: 10.3389/fmicb.2018.01040
    Zika virus (ZIKV) has emerged as a new global health threat. Since its first discovery in Zika forest in Uganda, this virus has been isolated from several mosquito species, including Aedes aegypti and Aedes albopictus. The geographical distribution of these mosquito species across tropical and subtropical regions has led to several outbreaks, including the recent pandemic in Brazil, followed by the Pacific islands and other areas of North and South America. This has gained attention of the scientific community to elucidate the epidemiology and transmission of ZIKV. Despite its strong attention on clinical aspects for healthcare professionals, the relationships between ZIKV and its principal vectors, A. aegypti and A. albopictus, have not gained substantial interest in the scientific research community. As such, this review aims to summarize the current knowledge on ZIKV tropism and some important mechanisms which may be employed by the virus for effective strategies on viral survival in mosquitoes. In addition, this review identifies the areas of research that should be placed attention to, for which to be exploited for novel mosquito control strategies.
  7. Hasebe F, Parquet MC, Pandey BD, Mathenge EG, Morita K, Balasubramaniam V, et al.
    J Med Virol, 2002 Jul;67(3):370-4.
    PMID: 12116030
    A reverse transcription-polymerase chain reaction (RT-PCR) was developed for the detection of Chikungunya virus infection. Based on the nonstructural protein 1 (nsP1) and glycoprotein E1 (E1) genes of Chikungunya, two primer sets were designed. Total RNA were extracted from the cell culture fluid of Aedes albopictus C6/36 cells inoculated with the S27 prototype virus, isolated in Tanzania in 1953, and the Malaysian strains (MALh0198, MALh0298, and MALh0398), isolated in Malaysia in 1998. For both sets of RNA samples, the expected 354- and 294-base pair (bp) cDNA fragments were amplified effectively from the nsP1 and E1 genes, respectively. Phylogenetic analysis was conducted for the Malaysian strain and other virus strains isolated from different regions in the world endemic for Chikungunya, using partial E1 gene sequence data. The Malaysian strains isolated during the epidemics of 1998 fell into a cluster with other members of the Asian genotype.
  8. Zulkiply SH, Balasubramaniam V, Abu Bakar NA, Abd Rashed A, Ismail SR
    PLoS One, 2019;14(8):e0220877.
    PMID: 31415611 DOI: 10.1371/journal.pone.0220877
    INTRODUCTION: Vegetable oil is an important source of fatty acids, and as palm oil being the highest consumed vegetable oil in many countries, its high saturated fatty acid content has led many concerns on cardiometabolic health. Dietary fatty acids has also been linked to affect glucose metabolism and insulin sensitivity. This systematic review is aimed at critically evaluating the available evidence on the association of palm oil with the biomarkers of glucose metabolism as compared to other vegetable oils.

    METHODS: We systemically searched PubMed, CENTRAL and Scopus up to June 2018. We searched for published interventional studies on biomarkers of glucose metabolism (defined as fasting glucose, fasting insulin, HOMA, 2-hour post prandial glucose and HbA1C) that compared palm oil- or palm olein-rich diets with other edible vegetable oils (such as olive oil, canola oil and soybean oil). Two reviewers independently extracted data and assessed study risks of bias. Mean differences of outcomes were pooled for the meta-analysis.

    RESULTS: We identified 1921 potentially eligible articles with only eight included studies. Seven randomised cross-over trials and one parallel trial were included. Study population were among young to middle-aged, healthy, non-diabetic, and normal weight participants. Intervention duration ranged from three to seven weeks, and fat substitution ranged from 15% to 20% energy. There were insignificant differences in fasting glucose when compared to partially hydrogenated soybean oil [-0.15mmol/L (-0.46,0.16) P = 0.33, I2 = 48%], soybean oil [0.05mmol/L (-0.09,0.18) P = 0.49, I2 = 0%] and olive oil [0.04mmol/L (-0.09,0.17) P = 0.76, I2 = 0%]. Insignificant effects were also seen on fasting insulin when compared to partially hydrogenated soybean oil [1.72pmol/L (-11.39,14.84) P = 0.80, I2 = 12%] and olive oil diet [-0.14pmol/L (-4.87,4.59) P = 0.95, I2 = 0%].

    CONCLUSION: Current evidence on the effects of palm oil consumption on biomarkers of glucose metabolism is poor and limited to only healthy participants. We conclude that little or no additional benefit will be obtained by replacing palm oil with other oils rich in mono or polyunsaturated fatty acids for changes in glucose metabolism.

  9. Arulsamy A, Tan QY, Balasubramaniam V, O'Brien TJ, Shaikh MF
    ACS Chem Neurosci, 2020 Nov 04;11(21):3488-3498.
    PMID: 33064448 DOI: 10.1021/acschemneuro.0c00431
    Dysbiosis of gut microbiota may lead to a range of diseases including neurological disorders. Thus, it is hypothesized that regulation of the intestinal microbiota may prevent or treat epilepsy. The purpose of this systematic review is to evaluate the evidence investigating the relationship between gut microbiota and epilepsy and possible interventions. A systematic review of the literature was done on four databases (PubMed, Scopus, EMBASE, and Web of Science). Study selection was restricted to original research articles while following the PRISMA guidelines. Six studies were selected. These studies cohesively support the interaction between gut microbiota and epileptic seizures. Gut microbiota analysis identified increases in Firmicutes, Proteobacteria, Verrucomicrobia, and Fusobacteria with decreases in Bacteroidetes and Actinobacteria in epileptic patients. Ketogenic diet, probiotics, and fecal microbiota transplantation (FMT) improved the dysbiosis of the gut microbiota and seizure activity. However, the studies either had a small sample size, lack of subject variability, or short study or follow-up period, which may question their reliability. Nevertheless, these limited studies conclusively suggest that gut microbiota diversity and dysbiosis may be involved in the pathology of epilepsy. Future studies providing more reliable and in depth insight into the gut microbial community will spark promising alternative therapies to current epilepsy treatment.
  10. Balasubramaniam V, Gunasegavan RD, Mustar S, Lee JC, Mohd Noh MF
    Molecules, 2021 Feb 10;26(4).
    PMID: 33579001 DOI: 10.3390/molecules26040943
    Microalgae are known as a rich source of bioactive compounds which exhibit different biological activities. Increased demand for sustainable biomass for production of important bioactive components with various potential especially therapeutic applications has resulted in noticeable interest in algae. Utilisation of microalgae in multiple scopes has been growing in various industries ranging from harnessing renewable energy to exploitation of high-value products. The focuses of this review are on production and the use of value-added components obtained from microalgae with current and potential application in the pharmaceutical, nutraceutical, cosmeceutical, energy and agri-food industries, as well as for bioremediation. Moreover, this work discusses the advantage, potential new beneficial strains, applications, limitations, research gaps and future prospect of microalgae in industry.
  11. Md Noh MF, Gunasegavan RD, Mustafa Khalid N, Balasubramaniam V, Mustar S, Abd Rashed A
    Molecules, 2020 Oct 06;25(19).
    PMID: 33036314 DOI: 10.3390/molecules25194567
    Food composition database (FCD) provides the nutritional composition of foods. Reliable and up-to date FCD is important in many aspects of nutrition, dietetics, health, food science, biodiversity, plant breeding, food industry, trade and food regulation. FCD has been used extensively in nutrition labelling, nutritional analysis, research, regulation, national food and nutrition policy. The choice of method for the analysis of samples for FCD often depends on detection capability, along with ease of use, speed of analysis and low cost. Sample preparation is the most critical stage in analytical method development. Samples can be prepared using numerous techniques; however it should be applicable for a wide range of analytes and sample matrices. There are quite a number of significant improvements on sample preparation techniques in various food matrices for specific analytes highlighted in the literatures. Improvements on the technology used for the analysis of samples by specific instrumentation could provide an alternative to the analyst to choose for their laboratory requirement. This review provides the reader with an overview of recent techniques that can be used for sample preparation and instrumentation for food analysis which can provide wide options to the analysts in providing data to their FCD.
  12. Lee LJ, Komarasamy TV, Adnan NAA, James W, Rmt Balasubramaniam V
    Front Immunol, 2021;12:750365.
    PMID: 34745123 DOI: 10.3389/fimmu.2021.750365
    Zika virus (ZIKV) received worldwide attention over the past decade when outbreaks of the disease were found to be associated with severe neurological syndromes and congenital abnormalities. Unlike most other flaviviruses, ZIKV can spread through sexual and transplacental transmission, adding to the complexity of Zika pathogenesis and clinical outcomes. In addition, the spread of ZIKV in flavivirus-endemic regions, and the high degree of structural and sequence homology between Zika and its close cousin Dengue have raised questions on the interplay between ZIKV and the pre-existing immunity to other flaviviruses and the potential immunopathogenesis. The Zika epidemic peaked in 2016 and has affected over 80 countries worldwide. The re-emergence of large-scale outbreaks in the future is certainly a possibility. To date, there has been no approved antiviral or vaccine against the ZIKV. Therefore, continuing Zika research and developing an effective antiviral and vaccine is essential to prepare the world for a future Zika epidemic. For this purpose, an in-depth understanding of ZIKV interaction with many different pathways in the human host and how it exploits the host immune response is required. For successful infection, the virus has developed elaborate mechanisms to escape the host response, including blocking host interferon response and shutdown of certain host cell translation. This review provides a summary on the key host factors that facilitate ZIKV entry and replication and the mechanisms by which ZIKV antagonizes antiviral innate immune response and involvement of adaptive immune response leading to immunopathology. We also discuss how ZIKV modulates the host immune response during sexual transmission and pregnancy to induce infection, how the cross-reactive immunity from other flaviviruses impacts ZIKV infection, and provide an update on the current status of ZIKV vaccine development.
  13. Lokman EF, Bugam SH, Ibrahim AS, Yunus N, Mansor F, Balasubramaniam V, et al.
    Nutr Health, 2023 Feb 08.
    PMID: 36755355 DOI: 10.1177/02601060231152060
    Introduction: The beneficial effects of resistant starch (RS) consumption on health in terms of reducing postprandial hyperglycaemia are evident. However, the potential of local Sarawak sago RS in regulating glucose has not been extensively studied. Objectives: This study aims to identify glucose-lowering effects of Sarawak sago RS, namely native (RS2) and chemically modified (RS4). Methodology: An oral glucose tolerance test (OGTT) was performed before and after 1 month treatment with sago RS2 and RS4 in spontaneously type 2 diabetes (T2D), Goto-Kakizaki (GK) rat. The mechanisms involved were further explored by screening the in vitro inhibitory activities of α-glucosidase and dipeptidyl peptidase (DPP)-IV. Histopathology examination for pancreas, kidney and liver tissues was done in response to sago RS intake using haematoxylin and eosin (H&E) staining. Results and discussion: The incremental area under the curve (iAUC) for blood glucose in RS-treated groups was decreased and significant in RS2-treated group (p 
  14. Jiang H, Bai L, Ji L, Bai Z, Su J, Qin T, et al.
    J Virol, 2020 07 16;94(15).
    PMID: 32461319 DOI: 10.1128/JVI.00294-20
    Japanese encephalitis virus (JEV) infection alters microRNA (miRNA) expression in the central nervous system (CNS). However, the mechanism contributing to miRNA regulation in the CNS is not known. We discovered global degradation of mature miRNA in mouse brains and neuroblastoma (NA) cells after JEV infection. Integrative analysis of miRNAs and mRNAs suggested that several significantly downregulated miRNAs and their targeted mRNAs were clustered into an inflammation pathway. Transfection with miRNA 466d-3p (miR-466d-3p) decreased interleukin-1β (IL-1β) expression and inhibited JEV replication in NA cells. However, miR-466d-3p expression increased after JEV infection in the presence of cycloheximide, indicating that viral protein expression reduced miR-466d-3p expression. We generated all the JEV coding proteins and demonstrated NS3 helicase protein to be a potent miRNA suppressor. The NS3 proteins of Zika virus, West Nile virus, and dengue virus serotype 1 (DENV-1) and DENV-2 also decreased miR-466d-3p expression. Results from helicase-blocking assays and in vitro unwinding assays demonstrated that NS3 could unwind pre-miR-466d and induce miRNA dysfunction. Computational models and an RNA immunoprecipitation assay revealed arginine-rich domains of NS3 to be crucial for pre-miRNA binding and degradation of host miRNAs. Importantly, site-directed mutagenesis of conserved residues in NS3 revealed that R226G and R202W reduced the binding affinity and degradation of pre-miR-466d. These results expand the function of flavivirus helicases beyond unwinding duplex RNA to degrade pre-miRNAs. Hence, we revealed a new mechanism for NS3 in regulating miRNA pathways and promoting neuroinflammation.IMPORTANCE Host miRNAs have been reported to regulate JEV-induced inflammation in the CNS. We found that JEV infection could reduce expression of host miRNA. The helicase region of the NS3 protein bound specifically to miRNA precursors and could lead to incorrect unwinding of miRNA precursors, thereby reducing the expression of mature miRNAs. This observation led to two major findings. First, our results suggested that JEV NS3 protein induced miR-466d-3p degradation, which promoted IL-1β expression and JEV replication. Second, arginine molecules on NS3 were the main miRNA-binding sites, because we demonstrated that miRNA degradation was abolished if arginines at R226 and R202 were mutated. Our study provides new insights into the molecular mechanism of JEV and reveals several amino acid sites that could be mutated for a JEV vaccine.
  15. Muñoz-Moreno R, Martínez-Romero C, Blanco-Melo D, Forst CV, Nachbagauer R, Benitez AA, et al.
    Cell Rep, 2019 12 17;29(12):3997-4009.e5.
    PMID: 31851929 DOI: 10.1016/j.celrep.2019.11.070
    Influenza A viruses (IAVs) have a remarkable tropism in their ability to circulate in both mammalian and avian species. The IAV NS1 protein is a multifunctional virulence factor that inhibits the type I interferon host response through a myriad of mechanisms. How NS1 has evolved to enable this remarkable property across species and its specific impact in the overall replication, pathogenicity, and host preference remain unknown. Here we analyze the NS1 evolutionary landscape and host tropism using a barcoded library of recombinant IAVs. Results show a surprisingly great variety of NS1 phenotypes according to their ability to replicate in different hosts. The IAV NS1 genes appear to have taken diverse and random evolutionary pathways within their multiple phylogenetic lineages. In summary, the high evolutionary plasticity of this viral protein underscores the ability of IAVs to adapt to multiple hosts and aids in our understanding of its global prevalence.
  16. Shah PS, Link N, Jang GM, Sharp PP, Zhu T, Swaney DL, et al.
    Cell, 2018 Dec 13;175(7):1931-1945.e18.
    PMID: 30550790 DOI: 10.1016/j.cell.2018.11.028
    Mosquito-borne flaviviruses, including dengue virus (DENV) and Zika virus (ZIKV), are a growing public health concern. Systems-level analysis of how flaviviruses hijack cellular processes through virus-host protein-protein interactions (PPIs) provides information about their replication and pathogenic mechanisms. We used affinity purification-mass spectrometry (AP-MS) to compare flavivirus-host interactions for two viruses (DENV and ZIKV) in two hosts (human and mosquito). Conserved virus-host PPIs revealed that the flavivirus NS5 protein suppresses interferon stimulated genes by inhibiting recruitment of the transcription complex PAF1C and that chemical modulation of SEC61 inhibits DENV and ZIKV replication in human and mosquito cells. Finally, we identified a ZIKV-specific interaction between NS4A and ANKLE2, a gene linked to hereditary microcephaly, and showed that ZIKV NS4A causes microcephaly in Drosophila in an ANKLE2-dependent manner. Thus, comparative flavivirus-host PPI mapping provides biological insights and, when coupled with in vivo models, can be used to unravel pathogenic mechanisms.
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