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microRNA expression and recurrence risk prediction in Triple Negative Breast Cancer patients

AbdulAziz A, MdSalleh M, Mohamad I, Bhavaraju V, Gan S, Ankathil R

Ann Oncol, 2017 Oct;28 Suppl 9:ix79.
PMID: 32120675 DOI: 10.1093/annonc/mdx697.022
Validation of a high-performance liquid chromatography method for tramadol and o-desmethyltramadol in human plasma using solid-phase extraction

Gan SH, Ismail R

J Chromatogr B Biomed Sci Appl, 2001 Aug 15;759(2):325-35.
PMID: 11499486

An HPLC system using solid-phase extraction and HPLC with UV detection has been validated in order to determine tramadol and o-desmethyltramadol (M1) concentrations in human plasma. The method developed was selective and linear for concentrations ranging from 50 to 3,500 ng/ml (tramadol) and 50 to 500 ng/ml (M1) with mean recoveries of 94.36 +/- 12.53% and 93.52 +/- 7.88%, respectively. Limit of quantitation (LOQ) was 50 ng/ml. For tramadol, the intra-day accuracy ranged from 95.48 to 114.64% and the inter-day accuracy, 97.21 to 103.24%. Good precision (0.51 and 18.32% for intra- and inter-day, respectively) was obtained at LOQ. The system has been applied to determine tramadol concentrations in human plasma samples for a pharmacokinetic study.
Utilisation of environmentally friendly okara-based biosorbent for cadmium(II) removal

Hiew BYZ, Lee LY, Lee XJ, Thangalazhy-Gopakumar S, Gan S

Environ Sci Pollut Res Int, 2021 Aug;28(30):40608-40622.
PMID: 32601866 DOI: 10.1007/s11356-020-09594-3

Heavy metals released by various industries are among the major pollutants found in water resources. In this research, biosorption technique was employed to remove cadmium (Cd2+) from an aqueous system using a novel biosorbent developed from okara waste (OW), a residue from soya bean-based food and beverage processing. Characterisation results revealed that the OW biosorbent contained functional groups such as hydroxyl-, carboxyl- and sulphur-based functional groups, and the surface of the biosorbent was rough with multiple fissures which might be the binding sites for the pollutant. The effects of dosage, solution pH, initial Cd2+ concentration, temperature and contact time were investigated using batch adsorption mode. The biosorption equilibrium and kinetic were best described by the Langmuir and Elovich models, respectively. The maximum biosorption capacities predicted by the Langmuir model were 10.91-14.80 mg/g at 30-70 °C, and the biosorption process was favourable as evident from 0 < RL < 1. The uptake of Cd2+ by the OW biosorbent was spontaneous and endothermic. The plausible biosorption mechanisms of this study could be ionic exchange, hydrogen bonding and electrostatic interactions. The Cd2+ loaded OW biosorbent could be regenerated using 0.4 M of HCl solution and regeneration was studied for 4 adsorption-desorption cycles. The present investigation supported that OW can be reused as a value-added biosorbent product for the removal of Cd2+ from the contaminated water.
Tunable durian seed gum-derived eutectogel as a novel coating material: Rheological, thermal, textural and barrier properties for enhanced food preservation

Chew ZL, Koh QQ, Chu EE, Kua YL, Gan S, Tan KW, et al.

Int J Biol Macromol, 2024 Mar 29;267(Pt 1):131201.
PMID: 38554921 DOI: 10.1016/j.ijbiomac.2024.131201

As a promising green and sustainable coating material, gum was extracted from durian seed to produce eutectogel, which the properties were tunable using natural deep eutectic solvent (NADES). Ten different eutectogels were successfully synthesized using durian seed gum (DSG) and xanthan gum (XG) gelators at different composition (5, 10, 15 %) to gel choline chloride-glucose (1:1), choline chloride-fructose (1:2) and betaine-glucose-water (1:1:1) NADESs. Results revealed that eutectogel was non-Newtonian and weak gel material with excellent thermostability up to 200 °C. When the gum content increased, the resulted eutectogel showed higher viscosity, yield stress, hardness, gumminess, adhesiveness, and weight holding capacity. In overall, choline chloride-fructose (1:2) NADES and 10 % of DSG formed an excellent eutectogel which remained stable and compatible upon 12 weeks of storage. It displayed superior viscoelastic, texture, gases and moisture barrier properties which were beneficial for food coating application. This eutectogel was able to extend the shelf life of fresh-cut apples during storage with lower weight loss and higher total phenolic content (TPC). The potential future of this well-characterized tunable DSG-derived eutectogel includes, but not limited to, food and pharmaceutical industries, smart sensing, flexible wearable electronics, water purification, supercapacitors and batteries.
The pattern and frequency of t(14;18) translocation and immunophenotype in Asian follicular lymphoma

Peh SC, Shaminie J, Tai YC, Tan J, Gan SS

Histopathology, 2004 Nov;45(5):501-10.
PMID: 15500654

Follicular lymphoma is frequently associated with t(14;18)(q32;q21) translocation. This study was undertaken to determine the pattern of Bcl-2, CD10 and Bcl-6 expression in relation to t(14;18) translocation in follicular lymphoma from a cohort of a multi-ethnic Asian population.
Synthesis of kenaf cellulose carbamate using microwave irradiation for preparation of cellulose membrane

Gan S, Zakaria S, Chia CH, Kaco H, Padzil FN

Carbohydr Polym, 2014 Jun 15;106:160-5.
PMID: 24721064 DOI: 10.1016/j.carbpol.2014.01.076

Cellulose carbamate (CCs) was produced from kenaf core pulp (KCP) using microwave reactor-assisted method. The effects of urea concentration and reaction time on the formation of nitrogen content in CCs were investigated. The CCs' solubility in LiOH/urea system was determined and its membranes were characterized. As the urea content and reaction time increased, the nitrogen content form in CCs increased which enhanced the CCs' solubility. The formation of CCs was confirmed by Fourier transform infrared spectroscopy (FT-IR) and nitrogen content analysis. The CCs' morphology was examined using Scanning electron microscopy (SEM). The cellulose II and crystallinity index of the membranes were confirmed by X-ray diffraction (XRD). The pore size of the membrane displayed upward trend with respect to the urea content observed under Field emission scanning electron microscope (FESEM). This investigation provides a simple and efficient procedure of CCs determination which is useful in producing environmental friendly regenerated CCs.
Synthesis of kenaf cellulose carbamate and its smart electric stimuli-response

Gan S, Piao SH, Choi HJ, Zakaria S, Chia CH

Carbohydr Polym, 2016 Feb 10;137:693-700.
PMID: 26686181 DOI: 10.1016/j.carbpol.2015.11.035

Cellulose carbamate (CC) was produced from kenaf core pulp (KCP) via a microwave reactor-assisted method. The formation of CC was confirmed by Fourier transform infrared spectroscopy and nitrogen content analysis. The degree of substitution, zeta potential and size distribution of CC were also determined. The CC was characterized with scanning electron microscopy, X-ray diffraction and thermogravimetry analysis. The CC particles were then dispersed in silicone oil to prepare CC-based anhydrous electric stimuli-responsive electrorheological (ER) fluids. Rhelogical measurement was carried out using rotational rheometer with a high voltage generator in both steady and oscillatory shear modes to examine the effect of electric field strength on the ER characteristics. The results showed that the increase in electric field strength has enhanced the ER properties of CC-based ER fluid due to the chain formation induced by electric polarization among the particles.
Superabsorbent hydrogel from oil palm empty fruit bunch cellulose and sodium carboxymethylcellulose

Salleh KM, Zakaria S, Sajab MS, Gan S, Kaco H

Int J Biol Macromol, 2019 Jun 15;131:50-59.
PMID: 30844455 DOI: 10.1016/j.ijbiomac.2019.03.028

A green regenerated superabsorbent hydrogel was fabricated with mixtures of dissolved oil palm empty fruit bunch (EFB) cellulose and sodium carboxymethylcellulose (NaCMC) in NaOH/urea system. The formation of hydrogel was aided with epichlorohydrin (ECH) as a crosslinker. The resultant regenerated hydrogel was able to swell >80,000% depending on the NaCMC concentrations. The hydrogel absorbed water rapidly upon exposure to water up to 48 h and gradually declined after 72 h. The crosslinked of covalent bond of COC between dissolved EFB cellulose (EFBC) with NaCMC was confirmed with Attenuated total reflectance Fourier transform infrared (ATR-FT-IR) spectroscopy. Crystallinity and thermal stability of the hydrogel samples were depended on the concentrations of NaCMC, crosslinking, and swelling process. The strength and stability of crosslinked network was studied by examining the gel fraction of hydrogel. This study explored the swelling ability and probable influenced factors towards physical and chemical properties of hydrogel.
Strategies for strengthening toughened poly(lactic acid) blend via natural reinforcement with enhanced biodegradability: A review

Shahdan D, Rosli NA, Chen RS, Ahmad S, Gan S

Int J Biol Macromol, 2023 Aug 11;251:126214.
PMID: 37572810 DOI: 10.1016/j.ijbiomac.2023.126214

The growing popularity of poly(lactic acid) (PLA) can be attributed to its favorable attributes, such as excellent compostability and robust mechanical properties. Two notable limitations of PLA are its high brittleness and slow biodegradation rate. Both of blending and copolymerization strategies work well to improve PLA's toughness while sacrificing the good tensile strength and modulus properties of PLA. One of the most effective and economical approaches to address this challenge is to incorporate natural reinforcing agents into the toughened PLA system, thereby simultaneously promoting the biodegradation rate of PLA. Nevertheless, the enhancement of tensile strength and modulus is accompanied by a notable decrease in elongation. Therefore, this review provides comprehensive information on the literature works related to the tensile strength, modulus, elongation at break and impact strength of the toughened PLA and its natural fiber reinforced composites. The impact of natural reinforcing agent on the tensile fracture mechanism as well as the synergistic effect on strengthening and toughening performance will be discussed. This review also focuses on the factors boosting the biodegradability of toughened PLA blend by using natural reinforcing fiber. Review presents potential future insights into the development of biodegradable and balanced strengthened-toughened PLA based advanced materials.
Stereoselective method development and validation for determination of concentrations of amphetamine-type stimulants and metabolites in human urine using a simultaneous extraction-chiral derivatization approach

Wan Raihana WA, Gan SH, Tan SC

J Chromatogr B Analyt Technol Biomed Life Sci, 2011 Jan 1;879(1):8-16.
PMID: 21147046 DOI: 10.1016/j.jchromb.2010.10.037

Amphetamine-type stimulants (ATS) are a group of chiral amine drugs which are commonly abused for their sympathomimetic and stimulant properties. ATS are extensively metabolised by hepatic cytochrome P450 enzymes. As metabolism of ATS has been shown to be highly stereospecific, stereoselective analytical methods are essential for the quantitative determination of ATS concentrations for both in vivo and in vitro studies of ATS metabolism. This paper describes a new stereoselective method for the simultaneous determination of amphetamine (AM), methamphetamine (MA), 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA), 4-hydroxy-3-methoxymethamphetamine (HMMA), 4-hydroxy-3-methoxyamphetamine (HMA), 3,4-hydroxymethamphetamine (HHMA) and 3,4-hydroxyamphetamine (HHA) in human urine samples validated according to the United States Food and Drug Administration guidelines. In this method, analytes are simultaneously extracted and derivatized with R-(-)-α-methoxy-α-(trifluoromethyl)phenylacetyl chloride (R-MTPCl) as the chiral derivatization reagent. Following this, the analytes were subjected to a second derivatization with N-methyl-N-trimethylsilyltrifluoroacetamide (MSTFA) which targets the hydroxyl groups present in HMMA, HMA, HHMA and HHA. The derivatized analytes were separated and quantified using gas chromatography-mass spectrometry (GC-MS). The method was evaluated according to the established guidelines for specificity, linearity, precision, accuracy, recovery and stability using a five-day protocol. Intra-day precision ranged from 0.89 to 11.23% RSD whereas inter-day precision was between 1.03 and 12.95% RSD. Accuracy values for the analytes ranged from -5.29% to 13.75%. Limits of quantitation were 10 μg/L for AM, MA, MDMA, HMA and HMMA and 2μg/L for MDA, HMA and HHA. Recoveries and stability values were also within accepted values. The method was applied to authentic ATS-positive samples.
Standard CYP2D6 genotyping procedures fail for the CYP2D6*5 and duplication alleles when hair roots are used as a source of DNA

Gan SH, Ismail R, Wan Adnan WA, Wan Z

Clin Chim Acta, 2003 Mar;329(1-2):61-8.
PMID: 12589966 DOI: 10.1016/s0009-8981(03)00019-6

BACKGROUND: Hair roots provide a useful alternative to blood as a source of DNA for genotyping. Besides simple and non-invasive collections, the DNA extraction step is also easy to perform and is fast. The aim of our study is to determine if hair roots can be used to genotype all of the common CYP2D6 alleles for routine screening purposes.

METHOD: The study complies with the Declaration of Helsinki. After obtaining informed consents, both blood and hair samples were collected from 92 patients for genotyping of the CYP2D6 gene. PCR was used to detect the following mutations: CYP2D6*1, *3, *4, *5, *9, *10, *17 and duplication gene. The results were compared where hair roots and blood were used as templates for DNA respectively.

RESULTS: When blood was used as a source of DNA for genotyping, all of the investigated CYP2D6 alleles were successfully amplified. However, with hair roots, the genes with the larger fragment sizes: CYP2D6*5 and the duplication gene could not be amplified and the bands of other alleles investigated were faint when visualized under UV light.

CONCLUSIONS: DNA extraction from hair roots and leucocytes yielded similar results but the DNA extracted from hair roots did not allow successful amplification of the longer genes such as the CYP2D6*5 and the duplication gene.
Single-nucleotide polymorphisms and mRNA expression of CYP1B1 influence treatment response in triple negative breast cancer patients undergoing chemotherapy

Abdul Aziz AA, Md Salleh MS, Mohamad I, Krishna Bhavaraju VM, Mazuwin Yahya M, Zakaria AD, et al.

J Genet, 2018 Dec;97(5):1185-1194.
PMID: 30555068

Triple negative breast cancer (TNBC) is typically associated with poor and interindividual variability in treatment response. Cytochrome P450 family 1 subfamily B1 (CYP1B1) is a metabolizing enzyme, involved in the biotransformation of xenobiotics and anticancer drugs. We hypothesized that, single-nucleotide polymorphisms (SNPs), CYP1B1 142 C>G, 4326 C>G and 4360 A>G, and CYP1B1 mRNA expression might be potential biomarkers for prediction of treatment response in TNBC patients. CYP1B1 SNPs genotyping (76 TNBC patients) was performed using allele-specific polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism methods and mRNA expression of CYP1B1 (41 formalin-fixed paraffin embeddedblocks) was quantified using quantitative reverse transcription PCR. Homozygous variant genotype (GG) and variant allele (G) of CYP1B1 4326C>G polymorphism showed significantly higher risk for development of resistance to chemotherapy with adjusted odds ratio (OR): 6.802 and 3.010, respectively. Whereas, CYP1B1 142 CG heterozygous genotype showed significant association with goodtreatment response with adjusted OR: 0.199. CYP1B1 142C-4326G haplotype was associated with higher risk for chemoresistance with OR: 2.579. Expression analysis revealed that the relative expression of CYP1B1 was downregulated (0.592) in cancerous tissue compared with normal adjacent tissues. When analysed for association with chemotherapy response, CYP1B1 expression was found to be significantly upregulated (3.256) in cancerous tissues of patients who did not respond as opposed to those of patients who showed response to chemotherapy. Our findings suggest that SNPs together with mRNA expression of CYP1B1 may be useful biomarkers to predict chemotherapy response in TNBC patients.
Signaling pathway genes for blood pressure, folate and cholesterol levels among hypertensives: an epistasis analysis

Wei LK, Menon S, Griffiths LR, Gan SH

J Hum Hypertens, 2015 Feb;29(2):99-104.
PMID: 25055800 DOI: 10.1038/jhh.2014.53

Irregular atrial pressure, defective folate and cholesterol metabolism contribute to the pathogenesis of hypertension. However, little is known about the combined roles of the methylenetetrahydrofolate reductase (MTHFR), apolipoprotein-E (ApoE) and angiotensin-converting enzyme (ACE) genes, which are involved in metabolism and homeostasis. The objective of this study is to investigate the association of the MTHFR 677 C>T and 1298A>C, ACE insertion-deletion (I/D) and ApoE genetic polymorphisms with hypertension and to further explore the epistasis interactions that are involved in these mechanisms. A total of 594 subjects, including 348 normotensive and 246 hypertensive ischemic stroke subjects were recruited. The MTHFR 677 C>T and 1298A>C, ACE I/D and ApoEpolymorphisms were genotyped and the epistasis interaction were analyzed. The MTHFR 677 C>T and ApoE polymorphisms demonstrated significant associations with susceptibility to hypertension in multiple logistic regression models, multifactor dimensionality reduction and a classification and regression tree. In addition, the logistic regression model demonstrated that significant interactions between the ApoE E3E3, E2E4, E2E2 and MTHFR 677 C>T polymorphisms existed. In conclusion, the results of this epistasis study indicated significant association between the ApoE and MTHFR polymorphisms and hypertension.
Fulltext Self-Reported Hypoglycemia in Insulin-Treated Patients with Diabetes: Results from the Philippine Cohort of the International Operations Hypoglycemia Assessment Tool (IO HAT) Study

Mirasol R, Nicodemus N, Jain A, Gadekar AV, Yu-Gan S

J ASEAN Fed Endocr Soc, 2018;33(1):12-21.
PMID: 33442106 DOI: 10.15605/jafes.033.01.03

Objective: To determine the frequency of hypoglycemia in insulin-treated patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) in the non-interventional International Operations Hypoglycemia Assessment Tool (IO HAT) study.
Methodology: This sub-analysis included Filipino patients with T1DM or T2DM, aged 18 years and older, treated with insulin for more than 12 months, who completed the two-part self-assessment questionnaires (SAQ1 and SAQ2) and patient diaries that recorded hypoglycemia during retrospective (6 months/4 weeks before baseline) and prospective period (4 weeks after baseline) (ClinicalTrials.gov number: NCT02306681).
Results: A total of 671 patients were enrolled and completed the SAQ1 (62 patients with T1DM and 609 patients with T2DM). Almost all patients (100% in T1DM and 99.3% in T2DM) experienced at least 1 hypoglycemic event prospectively. The incidence of any hypoglycemia was also high in the prospective period compared to retrospective period (72.6 [95% CI: 64.8, 80.9] events PPY and 43.6 [95% CI: 37.8, 49.9] events PPY; p=0.001, respectively) in T1DM patients.
Conclusion: Among insulin-treated patients, higher rates of hypoglycemia were reported prospectively than retrospectively. This indicates that the patients in real-life setting often under-report hypoglycemia. Patient education can help in accurate reporting and appropriate management of hypoglycemia and diabetes.
Remediation of soils contaminated with polycyclic aromatic hydrocarbons (PAHs)

Gan S, Lau EV, Ng HK

J Hazard Mater, 2009 Dec 30;172(2-3):532-49.
PMID: 19700241 DOI: 10.1016/j.jhazmat.2009.07.118

Polycyclic aromatic hydrocarbons (PAHs) are carcinogenic micropollutants which are resistant to environmental degradation due to their highly hydrophobic nature. Concerns over their adverse health effects have resulted in extensive studies on the remediation of soils contaminated with PAHs. This paper aims to provide a review of the remediation technologies specifically for PAH-contaminated soils. The technologies discussed here include solvent extraction, bioremediation, phytoremediation, chemical oxidation, photocatalytic degradation, electrokinetic remediation, thermal treatment and integrated remediation technologies. For each of these, the theories are discussed in conjunction with comparative evaluation of studies reported in the specialised literature.
Relationship between Type A and B personality and debrisoquine hydroxylation capacity

Gan SH, Ismail R, Wan Adnan WA, Zulmi W, Kumaraswamy N, Larmie ET

Br J Clin Pharmacol, 2004 Jun;57(6):785-9.
PMID: 15151524

A person with Type A personality is an 'aggressor' compared with the rarely harried Type B. Although debrisoquine hydroxylase (CYP2D6) capacity has been associated with personality, no study has specifically investigated its association with personality Type A and B. Therefore the aim of this research was to study the impact of CYP2D6 on Type A and B personality.
Quantitative determination of propranolol by ultraviolet HPLC in human plasma

Salman SA, Sulaiman SA, Ismail Z, Gan SH

Toxicol. Mech. Methods, 2010 Mar;20(3):137-42.
PMID: 20128736 DOI: 10.3109/15376511003602112

Many previous published methods for the quantitative determination of propranolol (PRN) in human plasma have poor recoveries and were not validated according to the FDA guideline. The aim of this study is to develop a simple HPLC method for detecting PRN in human plasma and to validate it so that it can be applied to a clinical study. Chromatographic separation was achieved using a mixture of a mobile phase consisting of 160 ml water, 180 ml methanol, 70 ml acetonitrile, 2.5 ml acetic acid, and 125 microl triethylamine (v/v). The pH of the whole mixture was adjusted to 3.4. A flow rate of 0.5 ml/min was employed throughout with a 15 microl injection volume. Detection was done using a UV detector at 291 nm. The validated method was linear for concentrations ranging from 15-180 ng/ ml with a good separation and specificity for both PRN and its internal standard, oxprenolol (OXP), with excellent recoveries, precision, and accuracies. The limit of detection (LOD) and limit of quantification (LOQ) were 1 and 10 ng/ml, respectively. The stability studies demonstrated that PRN is stable in the autosampler vials and also up to 3.5 months. To the authors' knowledge, the recovery, that ranged between 97.9-102.7%, is the highest among all previously reported methods that used HPLC with UV detection. The developed and validated method for PRN analysis is excellent and applicable to a clinical study.
Population pharmacokinetic modelling of tramadol with application of the NPEM algorithms

Gan SH, Ismail R, Wan Adnan WA, Zulmi W, Jelliffe RW

J Clin Pharm Ther, 2004 Oct;29(5):455-63.
PMID: 15482390

Although the kinetic behaviour of tramadol has been described, the present study is the first to our knowledge, to report specifically on the population pharmacokinetic modelling of tramadol hydrochloride.
Population pharmacokinetic modelling of repaglinide in healthy volunteers by using Non-Parametric Adaptive Grid Algorithm

Ruzilawati AB, Mohd Suhaimi AW, Gan SH

J Clin Pharm Ther, 2010 Feb;35(1):105-12.
PMID: 20175819 DOI: 10.1111/j.1365-2710.2009.01042.x

To estimate population pharmacokinetic parameters of repaglinide in 121 healthy Malaysian volunteers.
Polymethacrylate coated electrospun PHB fibers: An exquisite outlook for fabrication of paper-based biosensors

Hosseini S, Azari P, Farahmand E, Gan SN, Rothan HA, Yusof R, et al.

Biosens Bioelectron, 2015 Jul 15;69:257-64.
PMID: 25765434 DOI: 10.1016/j.bios.2015.02.034

Electrospun polyhydroxybutyrate (PHB) fibers were dip-coated by polymethyl methacrylate-co-methacrylic acid, poly(MMA-co-MAA), which was synthesized in different molar ratios of the monomers via free-radical polymerization. Fabricated platfrom was employed for immobilization of the dengue antibody and subsequent detection of dengue enveloped virus in enzyme-linked immunosorbent assay (ELISA). There is a major advantage for combination of electrospun fibers and copolymers. Fiber structre of electrospun PHB provides large specific surface area available for biomolecular interaction. In addition, polymer coated parts of the platform inherited the premanent presence of surface carboxyl (-COOH) groups from MAA segments of the copolymer which can be effectively used for covalent and physical protein immobilization. By tuning the concentration of MAA monomers in polymerization reaction the concentration of surface -COOH groups can be carefully controlled. Therefore two different techniques have been used for immobilization of the dengue antibody aimed for dengue detection: physical attachment of dengue antibodies to the surface and covalent immobilization of antibodies through carbodiimide chemistry. In that perspective, several different characterization techniques were employed to investigate the new polymeric fiber platform such as scanning electron microscopy (SEM), atomic force microscopy (AFM), water contact angle (WCA) measurement and UV-vis titration. Regardless of the immobilization techniques, substantially higher signal intensity was recorded from developed platform in comparison to the conventional ELISA assay.

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