Displaying publications 81 - 100 of 270 in total

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  1. The role of alternative salt bridges in cold adaptation of a novel psychrophilic laminarinase
    Parvizpour S, Razmara J, Shamsir MS, Illias RM, Abdul Murad AM
    J Biomol Struct Dyn, 2017 06;35(8):1685-1692.
    PMID: 27206405 DOI: 10.1080/07391102.2016.1191043
  2. Expression and characterization of a cellobiohydrolase (CBH7B) from the thermophilic fungus Thielavia terrestris in Pichia pastoris
    Woon JS, Mackeen MM, Mahadi NM, Illias RM, Abdul Murad AM, Abu Bakar FD
    Biotechnol Appl Biochem, 2016 Sep;63(5):690-698.
    PMID: 26265428 DOI: 10.1002/bab.1431
    The gene encoding a cellobiohydrolase 7B (CBH7B) of the thermophilic fungus Thielavia terrestris was identified, subcloned, and expressed in Pichia pastoris. CBH7B encoded 455 amino acid residues with a molecular mass of 51.8 kDa. Domain analysis indicated that CBH7B contains a family 7 glycosyl hydrolase catalytic core but lacks a carbohydrate-binding module. Purified CBH7B exhibited optimum catalytic activity at pH 5.0 and 55 °C with 4-methylumbelliferryl-cellobioside as the substrate and retained 85% of its activity following 24 H incubation at 50 °C. Despite the lack of activity toward microcrystalline substrates, this enzyme worked synergistically with the commercial enzyme cocktail Cellic(®) CTec2 to enhance saccharification by 39% when added to a reaction mixture containing 0.25% alkaline pretreated oil palm empty fruit bunch (OPEFB). Attenuated total reflectance Fourier transform infrared spectroscopy suggested a reduction of lignin and crystalline cellulose in OPEFB samples supplemented with CBH7B. Scanning electron microscopy revealed greater destruction extent of OPEFB strands in samples supplemented with CBH7B as compared with the nonsupplemented control. Therefore, CBH7B has the potential to complement commercial enzymes in hydrolyzing lignocellulosic biomass.
  3. Fulltext Recognizing rheumatoid arthritis: oncoprotein survivin opens new possibilities: a population-based case-control study
    Chun-Lai T, Murad S, Erlandsson MC, Hussein H, Sulaiman W, Dhaliwal JS, et al.
    Medicine (Baltimore), 2015 Jan;94(4):e468.
    PMID: 25634192 DOI: 10.1097/MD.0000000000000468
    Survivin is a biomarker of cancer known for its anti-apoptotic and cell-cycle regulating properties. In the context of non-cancer pathology, high levels of survivin may be measured in blood and synovial fluid of patients with rheumatoid arthritis (RA) and associate with early joint damage and poor therapy response. The aim of the study was to investigate the value of survivin measurements in blood for diagnosis of RA in the frame of the Malaysian epidemiological investigation of rheumatoid arthritis (MyEIRA) study. The study enrolled RA patients from eight rheumatology centres in Peninsular Malaysia. The healthy controls matched by age, gender and ethnicity were recruited on the community basis from the residential area of the patients. Levels of survivin were measured in blood of RA patients (n = 1233) and controls (n = 1566) by an enzyme-linked immuno-sorbent assay (ELISA). The risk for RA was calculated as odds ratio (OR) and 95% confidence intervals in the individuals with high levels of survivin. The risk was calculated in relation to antibodies against cyclic citrullinated peptides (ACPA), detected by ELISA and HLA-DRB1 shared epitope (SE) alleles, identified by the polymerase chain reaction using sequence specific oligonucleotide method. High levels of survivin were detected in 625 of 1233 (50.7%) RA cases and in 85 of 1566 (5.4%) controls, indicating its high specificity for RA. Survivin was association with an increase in RA risk in the patients having neither SE-alleles nor ACPA (OR = 5.40, 95% CI 3.81-7.66). For the patients combining survivin, SE, and ACPA, the estimated risk for RA was 16-folds higher compared to the survivin negative patients with SE and ACPA(OR = 16.21, 95% CI 5.70-46.18). To conclude, detection of survivin in blood provides a simple test to improve diagnostic and to increase predictability for RA.
  4. Fulltext Regulation of terpenoid biosynthesis by miRNA in Persicaria minor induced by Fusarium oxysporum
    Samad AFA, Rahnamaie-Tajadod R, Sajad M, Jani J, Murad AMA, Noor NM, et al.
    BMC Genomics, 2019 07 16;20(1):586.
    PMID: 31311515 DOI: 10.1186/s12864-019-5954-0
    BACKGROUND: Persicaria minor (kesum) is an herbaceous plant with a high level of secondary metabolite compounds, particularly terpenoids. These terpenoid compounds have well-established roles in the pharmaceutical and food industries. Although the terpenoids of P. minor have been studied thoroughly, the involvement of microRNA (miRNA) in terpenoid regulation remains poorly understood and needs to be explored. In this study, P. minor plants were inoculated with the pathogenic fungus Fusarium oxysporum for terpenoid induction.

    RESULT: SPME GC-MS analysis showed the highest terpenoid accumulation on the 6th day post-inoculation (dpi) compared to the other treatment time points (0 dpi, 3 dpi, and 9 dpi). Among the increased terpenoid compounds, α-cedrene, valencene and β-bisabolene were prominent. P. minor inoculated for 6 days was selected for miRNA library construction using next generation sequencing. Differential gene expression analysis showed that 58 miRNAs belonging to 30 families had significantly altered regulation.
    Among these 58 differentially expressed genes (DEGs), 27 [corrected] miRNAs were upregulated, whereas 31 [corrected] miRNAs were downregulated. Two putative novel pre-miRNAs were identified and validated through reverse transcriptase PCR. Prediction of target transcripts potentially involved in the mevalonate pathway (MVA) was carried out by psRobot software, resulting in four miRNAs: pmi-miR530, pmi-miR6173, pmi-miR6300 and a novel miRNA, pmi-Nov_13. In addition, two miRNAs, miR396a and miR398f/g, were predicted to have their target transcripts in the non-mevalonate pathway (MEP). In addition, a novel miRNA, pmi-Nov_12, was identified to have a target gene involved in green leaf volatile (GLV) biosynthesis. RT-qPCR analysis showed that pmi-miR6173, pmi-miR6300 and pmi-nov_13 were downregulated, while miR396a and miR398f/g were upregulated. Pmi-miR530 showed upregulation at 9 dpi, and dynamic expression was observed for pmi-nov_12. Pmi-6300 and pmi-miR396a cleavage sites were detected through degradome sequence analysis. Furthermore, the relationship between miRNA metabolites and mRNA metabolites was validated using correlation analysis.

    CONCLUSION: Our findings suggest that six studied miRNAs post-transcriptionally regulate terpenoid biosynthesis in P. minor. This regulatory behaviour of miRNAs has potential as a genetic tool to regulate terpenoid biosynthesis in P. minor.

  5. Fulltext Correction to: Regulation of terpenoid biosynthesis by miRNA in Persicaria minor induced by Fusarium oxysporum
    Samad AFA, Rahnamaie-Tajadod R, Sajad M, Jani J, Murad AMA, Noor NM, et al.
    BMC Genomics, 2019 08 01;20(1):627.
    PMID: 31370802 DOI: 10.1186/s12864-019-5994-5
    Following publication of the original article [1], the authors reported a number of errors, which are listed in this Correction article. The corrections are marked in bold.
  6. Improved Diagnosis of the Polysensitized Allergic Rhinitis Patients Using Component Resolved Diagnosis Method
    Mohamad Yadzir ZH, Bakhtiar F, Misnan R, Abdullah N, Leecyous B, Murad S
    Iran J Allergy Asthma Immunol, 2016 Apr;15(2):156-60.
    PMID: 27090369
    Allergy diagnosis needs to be improved in polysensitized patients due to the existence of possible confounding factors in this type of patients. Component resolved diagnosis (CRD) is a new concept in the investigation of polysensitized patients. The aim of this study was to evaluate if the utilization of ImmunoCAP ISAC improve the diagnosis of the polysensitized allergic rhinitis patients. Skin prick test (SPT) to 58 crude allergen extracts and CRD (ImmunoCAP ISAC) were carried out for 5 polysensitized allergic rhinitis patients. Two patients had a shellfish allergy and avoidance of shellfish was the only way to prevent an allergic reaction. In contrast, although the remaining three patients had low risk for shellfish allergy, but they were the best candidates for immunotherapy using mite extracts. CRD and particularly ImmunoCAP ISAC have proven to be a valuable diagnostic tool in polysensitized patients. ImmunoCAP ISAC helps refine the individual patient's sensitization profile and predict the potential risk of allergic reactions and improve the selection of patients for immunotherapy.
  7. Component-resolved diagnosis (CRD): Is it worth it? frequency and differentiation in rhinitis patients with mite reactivity
    Mohamad Yadzir ZH, Misnan R, Abdullah N, Bakhtiar F, Leecyous B, Murad S
    Iran J Allergy Asthma Immunol, 2014 Aug;13(4):240-6.
    PMID: 24659159
    Component-resolved diagnosis (CRD) using microarray technology has recently been introduced with the aim to improve diagnosis of allergy. The aim of this study was to compare performance of this allergen microarray to those of an established extract-based skin prick testing (SPT).45 patients with allergic rhinitis were studied (16 children and 29 adults). SPT to Dermatophagoides pteronyssinus, Dermatophagoides farinae and Blomia tropicalis extracts and allergen microarray ImmunoCAP ISAC were carried out for all patients. Forty out of 45 patients demonstrated positive SPT to all mite extracts tested. These 40 patients were considered to be mite-allergic based on the positive SPT results. The remaining 5 patients with negative SPT to any mite extracts were classified as non-mite allergic. Comparatively, based on the microarray results, only 34 mite-allergic patients had detectable serum IgE to at least one of the mite allergen components tested whereas 6 patients with positive SPT to mite extracts showed no detectable IgE reactivity to any of the components tested. One non-mite allergic patient had a positive test- Blo t 5. Der p 10-positive patients also reacted to other cross-reactive tropomyosin from anisakis (Ani s 3) (25%), cockroach (Bla g 7) (50%) and shrimp (Pen m 1) (75%). CRD is a reliable tool for the diagnosis of allergy to mites. Der p 10 might be a useful indicator to identify a subset of mite-allergic patient that have additional sensitization due to cross-reactivity and thus allows selection of patients for immunotherapy.
  8. Impacts of Thermal Treatments on Major and Minor Allergens of Sea Snail, Cerithidea obtusa (Obtuse Horn Shell)
    Misnan R, Salahudin Abd Aziz N, Mohamad Yadzir ZH, Bakhtiar F, Abdullah N, Murad S
    Iran J Allergy Asthma Immunol, 2016 Aug;15(4):309-316.
    PMID: 27921412
    Snail is one of the worst causes of food allergy. Thus, the aim of this study was to identify the major and minor allergens of the local marine snail (Cerithidea obtusa) and subsequently to investigate the impacts of heat treatment on the IgE-binding activity of snail allergens. Proteins from raw and heat-treated snails (boiled, roasted and fried) were extracted and then resolved by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). Immunoblotting of all extracts were then performed using sera from patients with snail allergy. The results showed that the raw extract contains numerous protein bands between 12 to>250 kDa. Some thermostable proteins, predominantly the 33 and 42 kDa bands, remained detected in all cooked extracts with decreasing intensities from boiled to roasted to fried extracts, while the majority of thermolabile bands denatured after heating. Boiled snail had more protein bands compared to roasted and fried snails. Immunoblotting of raw extract demostrated 19 IgE-binding bands ranging from 15 to 240 kDa. The thermostable bands of 33 and 42 kDa and a thermolabile of 30 kDa band were identified as the major allergens of this snail. The cooked extracts yielded less allergenic bands. The boiled extract yielded approximately 14 IgE-binding bands with some smeared bands at high molecular weight regions. The roasted extract had lesser IgE-binding bands and the majority appeared as smears, while the IgE-reactivity in the fried extract was less visible and appeared as weak smears. This study indicated that both raw and cooked snails played a crucial role in snail allergenicity, as this species of snail contains both thermostable and thermolabile major allergens. The degree of snail allergenicity was revealed in the order: raw> boiled > roasted> fried. Thus, the results would facilitate in the development of effective diagnosis and management strategies of snail allergy in this country.
  9. Doxorubicin and siRNA Codelivery via Chitosan-Coated pH-Responsive Mixed Micellar Polyplexes for Enhanced Cancer Therapy in Multidrug-Resistant Tumors
    Butt AM, Amin MC, Katas H, Abdul Murad NA, Jamal R, Kesharwani P
    Mol Pharm, 2016 12 05;13(12):4179-4190.
    PMID: 27934479
    This study investigated the potential of chitosan-coated mixed micellar nanocarriers (polyplexes) for codelivery of siRNA and doxorubicin (DOX). DOX-loaded mixed micelles (serving as cores) were prepared by thin film hydration method and coated with chitosan (CS, serving as outer shell), and complexed with multidrug resistance (MDR) inhibiting siRNA. Selective targeting was achieved by folic acid conjugation. The polyplexes showed pH-responsive enhanced DOX release in acidic tumor pH, resulting in higher intracellular accumulation, which was further augmented by downregulation of mdr-1 gene after treatment with siRNA-complexed polyplexes. In vitro cytotoxicity assay demonstrated an enhanced cytotoxicity in native 4T1 and multidrug-resistant 4T1-mdr cell lines, compared to free DOX. Furthermore, in vivo, polyplexes codelivery resulted in highest DOX accumulation and significantly reduced the tumor volume in mice with 4T1 and 4T1-mdr tumors as compared to the free DOX groups, leading to improved survival times in mice. In conclusion, codelivery of siRNA and DOX via polyplexes has excellent potential as targeted drug nanocarriers for treatment of MDR cancers.
  10. The use of salt-coating to improve textural, mechanical, cooking and sensory properties of air-dried yellow alkaline noodles
    Yeoh SY, Lubowa M, Tan TC, Murad M, Mat Easa A
    Food Chem, 2020 Dec 15;333:127425.
    PMID: 32683254 DOI: 10.1016/j.foodchem.2020.127425
    Zero-salted yellow alkaline noodles (YAN) were immersed in solutions of resistant starch HYLON™ VII (HC) or fruit coating Semperfresh™ (SC) containing a range of salt (NaCl) between 10 and 30% (w/v). The objective was to evaluate the effect of salt-coatings on the textural, handling, cooking, and sensory properties of YAN. Increasing salt in the coatings caused a reduction in optimum cooking time, cooking loss and increase in cooking yield. The mechanical and textural parameters, sensory hardness, springiness and overall sensory acceptability of the salt-coated noodles however decreased with increasing salt application. HC-Na10 and SC-Na10 showed the highest textural and mechanical parameters, sensory hardness and springiness. The differences in the parameters were attributed mainly to the water absorption properties of starch that was affected by salt application. Thus, the quality of salt-coated noodles was dependent mainly on the amounts of salt applied in the coatings rather than on the types of coatings used.
  11. Fulltext Polymorphisms in peptidylarginine deiminase associate with rheumatoid arthritis in diverse Asian populations: evidence from MyEIRA study and meta-analysis
    Too CL, Murad S, Dhaliwal JS, Larsson P, Jiang X, Ding B, et al.
    Arthritis Res Ther, 2012;14(6):R250.
    PMID: 23164236 DOI: 10.1186/ar4093
    INTRODUCTION: The majority of our knowledge regarding disease-related mechanisms of uncontrolled citrullination and anti-citrullinated protein antibody development in rheumatoid arthritis (RA) was investigated in Caucasian populations. However, peptidylarginine deiminase (PADI) type 4 gene polymorphisms are associated with RA in East Asian populations and weak or no association was found in Caucasian populations. This study explores the association between the PADI4 polymorphisms and RA risk in a multiethnic population residing in South East Asia with the goal of elucidating generalizability of association in non-Caucasian populations.
    METHODS: A total of 320 SNPs from the PADI locus (including PADI1, PADI2, PADI3, PADI4 and PADI6 genes) were genotyped in 1,238 RA cases and 1,571 control subjects from the Malaysian Epidemiological Investigation of Rheumatoid Arthritis (MyEIRA) case-control study. Additionally, we conducted meta-analysis of our data together with the previously published studies of RA from East Asian populations.
    RESULTS: The overall odds ratio (ORoverall) for the PADI4 (rs2240340) allelic model was 1.11 (95% confidence interval (CI) = 1.00 to 1.23, P = 0.04) and for the genotypic model was 1.20 (95% CI = 1.01 to 1.44, P = 0.04). Haplotype analysis for four selected PADI4 SNPs revealed a significant association of one with susceptibility (P = 0.001) and of another with a protective effect (P = 0.02). The RA susceptibility was further confirmed when combined meta-analysis was performed using these data together with data from five previously published studies from Asia comprising 5,192 RA cases and 4,317 control subjects (ORoverall = 1.23 (95% CI = 1.16 to 1.31, Pheterogeneity = 0.08) and 1.31 (95% CI = 1.20 to 1.44, Pheterogeneity = 0.32) in allele and genotype-based models, respectively). In addition, we also detected a novel association of PADI2 genetic variant rs1005753 with RA (ORoverall = 0.87 (95% CI = 0.77 to 0.99)).
    CONCLUSION: Our study demonstrates an association between PADI4 and RA in the multiethnic population from South East Asia and suggests additional association with a PADI2 gene. The study thus provides further support for the notion that polymorphisms in genes for enzymes responsible for citrullination contribute to RA development in multiple populations of Asian descent.
  12. Fulltext MicroRNA and Transcription Factor: Key Players in Plant Regulatory Network
    Samad AFA, Sajad M, Nazaruddin N, Fauzi IA, Murad AMA, Zainal Z, et al.
    Front Plant Sci, 2017;8:565.
    PMID: 28446918 DOI: 10.3389/fpls.2017.00565
    Recent achievements in plant microRNA (miRNA), a large class of small and non-coding RNAs, are very exciting. A wide array of techniques involving forward genetic, molecular cloning, bioinformatic analysis, and the latest technology, deep sequencing have greatly advanced miRNA discovery. A tiny miRNA sequence has the ability to target single/multiple mRNA targets. Most of the miRNA targets are transcription factors (TFs) which have paramount importance in regulating the plant growth and development. Various families of TFs, which have regulated a range of regulatory networks, may assist plants to grow under normal and stress environmental conditions. This present review focuses on the regulatory relationships between miRNAs and different families of TFs like; NF-Y, MYB, AP2, TCP, WRKY, NAC, GRF, and SPL. For instance NF-Y play important role during drought tolerance and flower development, MYB are involved in signal transduction and biosynthesis of secondary metabolites, AP2 regulate the floral development and nodule formation, TCP direct leaf development and growth hormones signaling. WRKY have known roles in multiple stress tolerances, NAC regulate lateral root formation, GRF are involved in root growth, flower, and seed development, and SPL regulate plant transition from juvenile to adult. We also studied the relation between miRNAs and TFs by consolidating the research findings from different plant species which will help plant scientists in understanding the mechanism of action and interaction between these regulators in the plant growth and development under normal and stress environmental conditions.
  13. Protein engineering of GH11 xylanase from Aspergillus fumigatus RT-1 for catalytic efficiency improvement on kenaf biomass hydrolysis
    Damis SIR, Murad AMA, Diba Abu Bakar F, Rashid SA, Jaafar NR, Illias RM
    Enzyme Microb Technol, 2019 Dec;131:109383.
    PMID: 31615675 DOI: 10.1016/j.enzmictec.2019.109383
    Enzyme hydrolysis faces a bottleneck due to the recalcitrance of the lignocellulose biomass. The protein engineering of GH11 xylanase from Aspergillus fumigatus RT-1 was performed near the active site and at the N-terminal region to improve its catalytic efficiency towards pretreated kenaf (Hibiscus cannabinus) hydrolysis. Five mutants were constructed by combined approaches of error-prone PCR, site-saturation and site-directed mutagenesis. The double mutant c168 t/Q192H showed the most effective hydrolysis reaction with a 13.9-fold increase in catalytic efficiency, followed by mutants Y7L and c168 t/Q192 H/Y7L with a 1.6-fold increase, respectively. The enhanced catalytic efficiency evoked an increase in sugar yield of up to 28% from pretreated kenaf. In addition, mutant c168 t/Q192 H/Y7L improved the thermostability at higher temperature and acid stability. This finding shows that mutations at distances less than 15 Å from the active site and at putative secondary binding sites affect xylanase catalytic efficiency towards insoluble substrates hydrolysis.
  14. Fulltext Occupational exposure to textile dust increases the risk of rheumatoid arthritis: results from a Malaysian population-based case-control study
    Too CL, Muhamad NA, Ilar A, Padyukov L, Alfredsson L, Klareskog L, et al.
    Ann Rheum Dis, 2016 06;75(6):997-1002.
    PMID: 26681695 DOI: 10.1136/annrheumdis-2015-208278
    OBJECTIVES: Lung exposures including cigarette smoking and silica exposure are associated with the risk of rheumatoid arthritis (RA). We investigated the association between textile dust exposure and the risk of RA in the Malaysian population, with a focus on women who rarely smoke.

    METHODS: Data from the Malaysian Epidemiological Investigation of Rheumatoid Arthritis population-based case-control study involving 910 female early RA cases and 910 female age-matched controls were analysed. Self-reported information on ever/never occupationally exposed to textile dust was used to estimate the risk of developing anti-citrullinated protein antibody (ACPA)-positive and ACPA-negative RA. Interaction between textile dust and the human leucocyte antigen DR β-1 (HLA-DRB1) shared epitope (SE) was evaluated by calculating the attributable proportion due to interaction (AP), with 95% CI.

    RESULTS: Occupational exposure to textile dust was significantly associated with an increased risk of developing RA in the Malaysian female population (OR 2.8, 95% CI 1.6 to 5.2). The association between occupational exposure to textile dust and risk of RA was uniformly observed for the ACPA-positive RA (OR 2.5, 95% CI 1.3 to 4.8) and ACPA-negative RA (OR 3.5, 95% CI 1.7 to 7.0) subsets, respectively. We observed a significant interaction between exposure to occupational textile dust and HLA-DRB1 SE alleles regarding the risk of ACPA-positive RA (OR for double exposed: 39.1, 95% CI 5.1 to 297.5; AP: 0.8, 95% CI 0.5 to 1.2).

    CONCLUSIONS: This is the first study demonstrating that textile dust exposure is associated with an increased risk for RA. In addition, a gene-environment interaction between HLA-DRB1 SE and textile dust exposure provides a high risk for ACPA-positive RA.
  15. Associated genetic polymorphisms and clinical manifestations in systemic lupus erythematosus in Asian populations - A systematic literature review
    Abd Talib AKA, Tan SC, Jamal R, Azizan EA, Shaharir SS, Abdul Murad NA
    Med J Malaysia, 2021 07;76(4):541-550.
    PMID: 34305116
    INTRODUCTION: Systemic lupus erythematosus (SLE) is a chronic and life-threatening autoimmune disease. Its prevalence and clinical manifestations are known to be particularly severe in the Asian populations. Although genetics is known to play an important role in SLE susceptibility and clinical manifestations, the specific polymorphisms associated with these phenotypes in Asia are unclear. Therefore, we aim to review the association of SLE genetic polymorphisms with lupus manifestations across Asian populations and their role in the pathogenesis of SLE.

    METHODS: A systematic search was conducted on PubMed, EBSCOHost, and Web of Science. We identified 22 casecontrol studies that matched our inclusion and exclusion criteria. Information such as study characteristics, genetic polymorphisms associated with SLE, and organ manifestations was extracted and reported in this review.

    RESULTS: In total, 30 polymorphisms in 16 genes were found to be associated with SLE among Asians. All included polymorphisms also reported associations with various SLE clinical features. The association of rs1234315 in TNFSF4 linking to SLE susceptibility (P=4.17x10-17 OR=1.45 95% CI=1.34-1.59) and musculoskeletal manifestation (P=3.35x10-9, OR=1.37, 95%CI= 1.23-1.51) might be the most potential biomarkers to differentiate SLE between Asian and other populations. In fact, these associated genetic variants were found in loci that were implicated in immune systems, signal transduction, gene expression that play important roles in SLE pathogenesis.

    DISCUSSIONS AND CONCLUSIONS: This review summarized the potential correlation between 30 genetic polymorphisms associated with SLE and its clinical manifestations among Asians. More efforts in dissecting the functional implications and linkage disequilibrium of associated variants may be required to validate these findings.

  16. Silencing of ZFP36L2 increases sensitivity to temozolomide through G2/M cell cycle arrest and BAX mediated apoptosis in GBM cells
    Che Mat MF, Mohamad Hanif EA, Abdul Murad NA, Ibrahim K, Harun R, Jamal R
    Mol Biol Rep, 2021 Feb;48(2):1493-1503.
    PMID: 33590411 DOI: 10.1007/s11033-021-06144-z
    Despite the advancements in primary brain tumour diagnoses and treatments, the mortality rate remains high, particularly in glioblastoma (GBM). Chemoresistance, predominantly in recurrent cases, results in decreased mean survival of patients with GBM. We aimed to determine the chemosensitisation and oncogenic characteristics of zinc finger protein 36-like 2 (ZFP36L2) in LN18 GBM cells via RNA interference (RNAi) delivery. We conducted a meta-analysis of microarray datasets and RNAi screening using pooled small interference RNA (siRNA) to identify the druggable genes responsive to GBM chemosensitivity. Temozolomide-resistant LN18 cells were used to evaluate the effects of gene silencing on chemosensitisation to the sub-lethal dose (1/10 of the median inhibitory concentration [IC50]) of temozolomide. ZFP36L2 protein expression was detected by western blotting. Cell viability, proliferation, cell cycle and apoptosis assays were carried out using commercial kits. A human apoptosis array kit was used to determine the apoptosis pathway underlying chemosensitisation by siRNA against ZFP36L2 (siZFP36L2). Statistical analyses were performed using one-way analysis of variance; p > 0.05 was considered significant. The meta-analysis and RNAi screening identified ZFP36L2 as a potential marker of GBM. ZFP36L2 knockdown significantly induced apoptosis (p 
  17. Retention of Somatic Memory Associated with Cell Identity, Age and Metabolism in Induced Pluripotent Stem (iPS) Cells Reprogramming
    Khoo TS, Jamal R, Abdul Ghani NA, Alauddin H, Hussin NH, Abdul Murad NA
    Stem Cell Rev Rep, 2020 04;16(2):251-261.
    PMID: 32016780 DOI: 10.1007/s12015-020-09956-x
    The discovery of induced pluripotent stem (iPS) cells in 2006 marked a major breakthrough in regenerative medicine, enabling reversal of terminally differentiated somatic cells into pluripotent stem cells. The embryonic stem (ES) cells-like pluripotency and unlimited self-renewal capability of iPS cells have granted them enormous potential in many applications, particularly regenerative therapy. Unlike ES cells, however, iPS cells exhibit somatic memories which were carried over from the tissue of origin thus limited its translation in clinical applications. This review provides an updated overview of the retention of various somatic memories associated with the cellular identity, age and metabolism of tissue of origin in iPS cells. The influence of cell types, stage of maturation, age and various other factors on the retention of somatic memory has been discussed. Recent evidence of somatic memory in the form of epigenetic, transcriptomic, metabolic signatures and its functional manifestations in both in vitro and in vivo settings also have been reviewed. The increasing number of studies which had adopted isogenic cell lines for comparisons in recent years had facilitated the identification of genuine somatic memories. These memories functionally affect iPS cells and its derivatives and are potentially tumorigenic thus, raising concerns on their safety in clinical application. Various approaches for memory erasure had since being reported and their efficacies were highlighted in this review.
  18. Structural and functional characterisation of a cold-active yet heat-tolerant dehydroquinase from Glaciozyma antarctica PI12
    Jaafar NR, Mahadi NM, Mackeen MM, Illias RM, Murad AMA, Abu Bakar FD
    J Biotechnol, 2021 Mar 10;329:118-127.
    PMID: 33539893 DOI: 10.1016/j.jbiotec.2021.01.019
    Dehydroquinase or 3-dehydroquinate dehydratase (DHQD) reversibly cleaves 3-dehydroquinate to form 3-dehydroshikimate. Here, we describe the functional and structural features of a cold active type II 3-dehydroquinate dehydratase from the psychrophilic yeast, Glaciozyma antarctica PI12 (GaDHQD). Functional studies showed that the enzyme was active at low temperatures (10-30 °C), but displayed maximal activity at 40 °C. Yet the enzyme was stable over a wide range of temperatures (10-70 °C) and between pH 6.0-10.0 with an optimum pH of 8.0. Interestingly, the enzyme was highly thermo-tolerant, denaturing only at approximately 84 °C. Three-dimensional structure analyses showed that the G. antarctica dehydroquinase (GaDHQD) possesses psychrophilic features in comparison with its mesophilic and thermophilic counterparts such as higher numbers of non-polar residues on the surface, lower numbers of arginine and higher numbers of glycine-residues with lower numbers of hydrophobic interactions. On the other hand, GaDHQD shares some traits (i.e. total number of hydrogen bonds, number of proline residues and overall folding) with its mesophilic and thermophilic counterparts. Combined, these features contribute synergistically towards the enzyme's ability to function at both low and high temperatures.
  19. Structure Prediction of a Novel Exo-β-1,3-Glucanase: Insights into the Cold Adaptation of Psychrophilic Yeast Glaciozyma antarctica PI12
    Mohammadi S, Parvizpour S, Razmara J, Abu Bakar FD, Illias RM, Mahadi NM, et al.
    Interdiscip Sci, 2018 Mar;10(1):157-168.
    PMID: 27475956 DOI: 10.1007/s12539-016-0180-9
    We report a detailed structural analysis of the psychrophilic exo-β-1,3-glucanase (GaExg55) from Glaciozyma antarctica PI12. This study elucidates the structural basis of exo-1,3-β-1,3-glucanase from this psychrophilic yeast. The structural prediction of GaExg55 remains a challenge because of its low sequence identity (37 %). A 3D model was constructed for GaExg55. Threading approach was employed to determine a suitable template and generate optimal target-template alignment for establishing the model using MODELLER9v15. The primary sequence analysis of GaExg55 with other mesophilic exo-1,3-β-glucanases indicated that an increased flexibility conferred to the enzyme by a set of amino acids substitutions in the surface and loop regions of GaExg55, thereby facilitating its structure to cold adaptation. A comparison of GaExg55 with other mesophilic exo-β-1,3-glucanases proposed that the catalytic activity and structural flexibility at cold environment were attained through a reduced amount of hydrogen bonds and salt bridges, as well as an increased exposure of the hydrophobic side chains to the solvent. A molecular dynamics simulation was also performed using GROMACS software to evaluate the stability of the GaExg55 structure at varying low temperatures. The simulation result confirmed the above findings for cold adaptation of the psychrophilic GaExg55. Furthermore, the structural analysis of GaExg55 with large catalytic cleft and wide active site pocket confirmed the high activity of GaExg55 to hydrolyze polysaccharide substrates.
  20. Fulltext Data for proteome analysis of Bacillus lehensis G1 in starch-containing medium
    Ling HL, Rahmat Z, Murad AMA, Mahadi NM, Illias RM
    Data Brief, 2017 Oct;14:35-40.
    PMID: 28761915 DOI: 10.1016/j.dib.2017.07.026
    Bacillus lehensis G1 is a cyclodextrin glucanotransferase (CGTase) producer, which can degrade starch into cyclodextrin. Here, we present the proteomics data of B. lehensis cultured in starch-containing medium, which is related to the article "Proteome-based identification of signal peptides for improved secretion of recombinant cyclomaltodextrin glucanotransferase in Escherichia coli" (Ling et. al, in press). This dataset was generated to better understand the secretion of proteins involved in starch utilization for bacterial sustained growth. A 2-DE proteomic technique was used and the proteins were tryptically digested followed by detection using MALDI-TOF/TOF. Proteins were classified into functional groups using the information available in SubtiList webserver (http://genolist.pasteur.fr/SubtiList/).
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