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Electrochemical Long Period Fiber Grating Sensing for Electroactive Species

Okazaki T, Orii T, Tan SY, Watanabe T, Taguchi A, Rahman FA, et al.

Anal Chem, 2020 07 21;92(14):9714-9721.
PMID: 32551577 DOI: 10.1021/acs.analchem.0c01062

We present an electrochemical long period fiber grating (LPFG) sensor for electroactive species with an optically transparent electrode. The sensor was fabricated by coating indium tin oxide onto the surface of LPFG using a polygonal barrel-sputtering method. LPFG was produced by an electric arc-induced technique. The sensing is based on change in the detection of electron density on the electrode surface during potential application and its reduction by electrochemical redox of analytes. Four typical electroactive species of methylene blue, hexaammineruthenium(III), ferrocyanide, and ferrocenedimethanol were used to investigate the sensor performance. The concentrations of analytes were determined by the modulation of the potential as the change in transmittance around the resonance band of LPFG. The sensitivity of the sensor, particularly to methylene blue, was high, and the sensor responded to a wide concentration range of 0.001 mM to 1 mM.
Study of the CTLA-4 gene polymorphisms in systemic lupus erythematosus (SLE) samples from Malaysia

Chua KH, Puah SM, Chew CH, Tan SY, Lian LH

Ann Hum Biol, 2010 Apr;37(2):274-80.
PMID: 19951233 DOI: 10.3109/03014460903325185

In this study, we investigated the polymorphisms of the exon 1 (+49A/G), promoter sites (-1722T/C, -1661A/G, -318C/T), and 3'-untranslated region (3'-UTR) (+6230 A/G) of the CTLA-4 gene in systemic lupus erythematosus (SLE) affected patients. Polymerase chain reaction-restriction fragment length polymorphism was used to determine genotypes of these five markers in 130 SLE patients and 130 healthy controls. Of the five tested polymorphisms, there was no statistical significant difference between the genotypic and allelic frequencies of patients with SLE and controls. Hence, we propose that the CTLA-4 gene does not play a major role in the genetic susceptibility to the development of SLE in the Malaysian population.
Differential effects of ketoconazole and primaquine on the pharmacokinetics and tissue distribution of imatinib in mice

Soo GW, Law JH, Kan E, Tan SY, Lim WY, Chay G, et al.

Anticancer Drugs, 2010 Aug;21(7):695-703.
PMID: 20629201

Imatinib, a selective inhibitor of c-KIT and Bcr-Abl tyrosine kinases, approved for the treatment of chronic myelogenous leukemia and gastrointestinal stromal tumors, shows further therapeutic potential for gliomas, glioblastoma, renal cell carcinoma, autoimmune nephritis and other neoplasms. It is metabolized by CYP3A4, is highly bound to alpha-1-acid glycoprotein and is a P-glycoprotein substrate limiting its brain distribution. We assess imatinib's protein binding interaction with primaquine, which also binds to alpha-1-acid glycoprotein, and its metabolic interaction with ketoconazole, which is a CYP3A4 inhibitor, on its pharmacokinetics and biodistribution. Male ICR mice, 9-12 weeks old were given imatinib PO (50 mg/kg) alone or co-administered with primaquine (12.5 mg/kg), ketoconazole (50 mg/kg) or both, and imatinib concentration in the plasma, kidney, liver and brain was measured at prescheduled time points by HPLC. Noncompartmental pharmacokinetic parameters were estimated. Primaquine increased 1.6-fold plasma AUC(0)--> infinity, C(Max) decreased 24%, T(Max) halved and t(1/2) and mean residence time were longer. Ketoconazole increased plasma AUC(0)-->infinity 64% and doubled the C(Max), but this dose did not affect t(1/2) or mean residence time. When ketoconazole and primaquine were co-administered, imatinib AUC(0)-->infinity and C(Max) increased 32 and 35%, respectively. Ketoconazole did not change imatinib's distribution efficiency in the liver and kidney, primaquine increased it two-fold and it was larger when both the drugs were co-administered with imatinib. Ketoconazole did not change brain penetration but primaquine increased it approximately three-fold. Ketoconazole and primaquine affect imatinib clearance, bioavailability and distribution pattern, which could improve the treatment of renal and brain tumors, but also increase toxicity. This would warrant hepatic and renal functions monitoring.
Fulltext Antioxidant Content, Antioxidant Activity, and Antibacterial Activity of Five Plants from the Commelinaceae Family

Tan JB, Yap WJ, Tan SY, Lim YY, Lee SM

Antioxidants (Basel), 2014 Nov 17;3(4):758-69.
PMID: 26785239 DOI: 10.3390/antiox3040758

Commelinaceae is a family of herbaceous flowering plants with many species used in ethnobotany, particularly in South America. However, thus far reports of their bioactivity are few and far between. The primary aim of this study was to quantify the antioxidant and antibacterial activity of five Commelinaceae methanolic leaf extracts. The antioxidant content was evaluated by the total phenolic content (TPC), total tannin content (TTC), and total flavonoid content (TFC) assays. The antioxidant activities measured were DPPH free radical scavenging (FRS), ferric reducing power (FRP), and ferrous ion chelating (FIC); of the five plants, the methanolic leaf extract of Tradescantia zebrina showed the highest antioxidant content and activity, and exhibited antibacterial activity against six species of Gram-positive and two species of Gram-negative bacteria in a range of 5-10 mg/mL based on the broth microdilution method.
Views and experiences of Malaysian family medicine trainees of female sexual dysfunction

Lai PS, Tan SY, Liew SM

Arch Sex Behav, 2016 Nov;45(8):2081-2089.
PMID: 27502351 DOI: 10.1007/s10508-016-0796-1

Sociocultural factors have been shown to be important influencers of sexual health and sexuality. Hence, the aim of our study was to explore the views and experiences of family medicine trainees regarding female sexual dysfunction (FSD) with a focus on the barriers and facilitators towards the initiation of conversation on this topic. A qualitative study design involving semi-structured focus group discussions (FGDs) was conducted with 19 family medicine trainees in Malaysia. The conceptual framework used was based on the Theory of Planned Behavior. Thematic approach was used to analyze the data. Participants perceived FSD as being uncommon and unimportant. According to our participants, patients often presented with indirect complaints, and doctors were not proactive in asking about FSD. Three main barriers were identified: doctor factors, perceived patient factors, and system factors. Lack of confidence, knowledge, experience, time, and embarrassment were the key barriers identified at the doctors' level. Lack of awareness, among patients regarding FSD, and local cultural and religious norms were the perceived patient barriers. System barriers were lack of time and privacy. Various facilitators, such as continuous medical education and public forums, were suggested as means to encourage family medicine trainees to initiate discussion on sexual matters during consultations. In conclusion, family medicine trainees found it difficult to initiate conversation on FSD with patients. Interventions to encourage conversation on FSD should target this and other identified barriers.
Fulltext Breakfast consumption among Malaysian primary and secondary school children and relationship with body weight status - Findings from the MyBreakfast Study

Tee ES, Nurliyana AR, Norimah AK, Mohamed HJBJ, Tan SY, Appukutty M, et al.

Asia Pac J Clin Nutr, 2018 2 1;27(2):421-432.
PMID: 29384332 DOI: 10.6133/apjcn.062017.12

BACKGROUND AND OBJECTIVES: This study aimed to determine the relationship between breakfast consumption and body weight status among primary and secondary school children in Malaysia.
METHODS AND STUDY DESIGN: This nationwide cross-sectional study involved 5,332 primary school children aged 6 to 12 years and 3,000 secondary school children aged 13 to 17 years. Height and weight were measured and BMI-for-age was determined. Socio-demographic backgrounds, breakfast habits and physical activity levels were assessed using questionnaires. Breakfast frequency was defined as follows: breakfast skippers (ate breakfast 0-2 days/week), irregular breakfast eaters (ate breakfast 3-4 days/week) and regular breakfast eaters (ate breakfast ≥5 days/week).
RESULTS: The overall prevalence of breakfast skippers and irregular breakfast eaters was 11.7% and 12.7% respectively. Breakfast skipping was related to age, sex, ethnicity, income and physical activity level. Among primary school boys and secondary school girls, the proportion of overweight/obesity was higher among breakfast skippers (boys: 43.9%, girls: 30.5%) than regular breakfast eaters (boys: 31.2%, girls: 22.7%). Among primary school children, only boys who skipped breakfast had a higher mean BMI-for-age z-score than regular breakfast eaters. Among secondary school boys and girls, BMI-for-age z-score was higher among breakfast skippers than regular breakfast eaters. Compared to regular breakfast eaters, primary school boys who skipped breakfast were 1.71 times (95% CI=1.26-2.32, p=0.001) more likely to be overweight/obese, while the risk was lower in primary school girls (OR=1.36, 95% CI=1.02-1.81, p=0.039) and secondary school girls (OR=1.38, 95% CI=1.01-1.90, p=0.044).
CONCLUSION: Regular breakfast consumption was associated with a healthier body weight status and is a dietary behaviour which should be encouraged.
Colorectal carcinoma in Malaysians: DNA mismatch repair pattern in a multiethnic population

Cheah PL, Looi LM, Teoh KH, Rahman NA, Wong LX, Tan SY

Asian Pac J Cancer Prev, 2014;15(7):3287-91.
PMID: 24815484

BACKGROUND: The interesting preponderance of Chinese with colorectal carcinoma (CRC) amongst the three major ethnic groups in Malaysia prompted a study to determine DNA mismatch repair (MMR) status in our CRC and attempt correlation with patient age, gender and ethnicity as well as location, grade, histological type and stage of tumour. Histologically re-confirmed CRC, diagnosed between 1st January 2005 and 31st December 2007 at the Department of Pathology, University of Malaya Medical Centre, were immunohistochemically stained with monoclonal antibodies to MMR proteins, MLH1, MSH2, MSH6 and PMS2 on the Ventana Benchmark XT autostainer. Of the 142 CRC cases entered into the study, there were 82 males and 60 females (M:F=1.4:1). Ethnically, 81 (57.0%) were Chinese, 32 (22.5%) Malays and 29 (20.4%) Indians. The patient ages ranged between 15-87 years (mean=62.4 years) with 21 cases <50-years and 121 ≥50-years of age. 14 (9.9%) CRC showed deficient MMR (dMMR). Concurrent loss of MLH1 and PMS2 occurred in 10, MSH2 and MSH6 in 2 with isolated loss of MSH6 in 1 and PMS2 in 1. dMMR was noted less frequently amongst the Chinese (6.2%) in comparison with their combined Malay and Indian counterparts (14.8%), and was associated with right sided and poorly differentiated tumours (p<0.05). 3 of the 5 (60.0%) dMMR CRC cases amongst the Chinese and 1 of 9 cases (11.1%) amongst the combined Malay and Indian group were <50-years of age. No significant association of dMMR was noted with patient age and gender, tumour stage or mucinous type.
Fulltext YersiniaBase: a genomic resource and analysis platform for comparative analysis of Yersinia

Tan SY, Dutta A, Jakubovics NS, Ang MY, Siow CC, Mutha NV, et al.

BMC Bioinformatics, 2015;16:9.
PMID: 25591325 DOI: 10.1186/s12859-014-0422-y

Yersinia is a Gram-negative bacteria that includes serious pathogens such as the Yersinia pestis, which causes plague, Yersinia pseudotuberculosis, Yersinia enterocolitica. The remaining species are generally considered non-pathogenic to humans, although there is evidence that at least some of these species can cause occasional infections using distinct mechanisms from the more pathogenic species. With the advances in sequencing technologies, many genomes of Yersinia have been sequenced. However, there is currently no specialized platform to hold the rapidly-growing Yersinia genomic data and to provide analysis tools particularly for comparative analyses, which are required to provide improved insights into their biology, evolution and pathogenicity.
Fulltext HelicoBase: a Helicobacter genomic resource and analysis platform

Choo SW, Ang MY, Fouladi H, Tan SY, Siow CC, Mutha NV, et al.

BMC Genomics, 2014;15:600.
PMID: 25030426 DOI: 10.1186/1471-2164-15-600

Helicobacter is a genus of Gram-negative bacteria, possessing a characteristic helical shape that has been associated with a wide spectrum of human diseases. Although much research has been done on Helicobacter and many genomes have been sequenced, currently there is no specialized Helicobacter genomic resource and analysis platform to facilitate analysis of these genomes. With the increasing number of Helicobacter genomes being sequenced, comparative genomic analysis on members of this species will provide further insights on their taxonomy, phylogeny, pathogenicity and other information that may contribute to better management of diseases caused by Helicobacter pathogens.
Fulltext Development of ListeriaBase and comparative analysis of Listeria monocytogenes

Tan MF, Siow CC, Dutta A, Mutha NV, Wee WY, Heydari H, et al.

BMC Genomics, 2015;16:755.
PMID: 26444974 DOI: 10.1186/s12864-015-1959-5

Listeria consists of both pathogenic and non-pathogenic species. Reports of similarities between the genomic content between some pathogenic and non-pathogenic species necessitates the investigation of these species at the genomic level to understand the evolution of virulence-associated genes. With Listeria genome data growing exponentially, comparative genomic analysis may give better insights into evolution, genetics and phylogeny of Listeria spp., leading to better management of the diseases caused by them.
Fulltext Characteristics associated with the consumption of malted drinks among Malaysian primary school children: findings from the MyBreakfast study

Jan Mohamed HJ, Loy SL, Mohd Taib MN, Karim NA, Tan SY, Appukutty M, et al.

BMC Public Health, 2015;15:1322.
PMID: 26718818 DOI: 10.1186/s12889-015-2666-5

The consumption of beverages contributes to diet quality and overall nutrition. Studies on malted drinks, one of the widely consumed beverage choices among children in Asia, however, have received limited attention. This study aimed to examine the prevalence of malted drink consumption and explored associations of sociodemographic characteristics, nutrient intakes, weight status and physical activity levels with malted drink consumption among primary school children in Malaysia.
Fulltext Erratum to: 'Characteristics associated with the consumption of malted drinks among Malaysian primary school children: findings from the MyBreakfast study'

Jan Mohamed HJ, Loy SL, Taib MN, Karim NA, Tan SY, Appukutty M, et al.

BMC Public Health, 2016;16:162.
PMID: 26883422 DOI: 10.1186/s12889-016-2745-2
Fulltext Interleukin-6 promoter polymorphisms (-174 G/C) in Malaysian patients with systemic lupus erythematosus

Chua KH, Kee BP, Tan SY, Lian LH

Braz. J. Med. Biol. Res., 2009 Jun;42(6):551-5.
PMID: 19448905 DOI: 10.1590/s0100-879x2009000600012

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that involves the inflammation of various organs upon deposition of immune complexes and is characterized by uncontrolled B cell hyperactivity. Despite intensive research on the etiology of the disease, the exact cause of the onset of SLE is unknown. The pathogenesis of the disease has been proposed to be associated with the imbalance of T helper type 1 (Th1) and Th2 cytokine activities. Elevated serum levels of interleukin-6 (IL-6), a Th2 cytokine with various functions in the regulation of human biological systems, are observed in SLE patients. In the present study, 100 Malaysian SLE patients and 100 controls were evaluated in order to determine the association of polymorphisms existing in the promoter region of the IL-6 gene with the onset of SLE. The homozygous G genotype was found to be significant in SLE patients (chi(2) = 33.754; P = 0.00000000625), whereas the heterozygous G/C genotype was significant in the controls (chi(2)= 25.087; P = 0.000000548). We suggest that the C allele might have a masking effect on the G allele when both alleles are present in heterozygous individuals. However, we did not observe any significant association of the homozygous C allele with the onset of SLE or with protection from the disease (chi(2) = 1.684; P = 0.194366).
Sunitinib DDI with paracetamol, diclofenac, mefenamic acid and ibuprofen shows sex-divergent effects on the tissue uptake and distribution pattern of sunitinib in mice

Tan SY, Wong MM, Tiew AL, Choo YW, Lim SH, Ooi IH, et al.

Cancer Chemother Pharmacol, 2016 10;78(4):709-18.
PMID: 27495788 DOI: 10.1007/s00280-016-3120-9

PURPOSE: Pharmacokinetic interaction of sunitinib with diclofenac, paracetamol, mefenamic acid and ibuprofen was evaluated due to their P450 mediated metabolism and OATP1B1, OATP1B3, ABCB1, ABCG2 transporters overlapping features.
METHODS: Male and female mice were administered 6 sunitinib doses (60 mg/kg) PO every 12 h and 30 min before the last dose were administered vehicle (control groups), 250 mg/kg paracetamol, 30 mg/kg diclofenac, 50 mg/kg mefenamic acid or 30 mg/kg ibuprofen (study groups), euthanized 6 h post last administration and sunitinib plasma, liver, kidney, brain concentrations analyzed.
RESULTS: Ibuprofen halved sunitinib plasma concentration in female mice (p
Fulltext Tissue-Specific microRNA Expression Profiling to Derive Novel Biomarkers for the Diagnosis and Subtyping of Small B-Cell Lymphomas

Hue SS, Jin Y, Cheng H, Bin Masroni MS, Tang LWT, Ho YH, et al.

Cancers (Basel), 2023 Jan 10;15(2).
PMID: 36672402 DOI: 10.3390/cancers15020453

Accurate diagnosis of the most common histological subtypes of small B-cell lymphomas is challenging due to overlapping morphological features and limitations of ancillary testing, which involves a large number of immunostains and molecular investigations. In addition, a common diagnostic challenge is to distinguish reactive lymphoid hyperplasia that do not require additional stains from such lymphomas that need ancillary investigations. We investigated if tissue-specific microRNA (miRNA) expression may provide potential biomarkers to improve the pathology diagnostic workflow. This study seeks to distinguish reactive lymphoid proliferation (RL) from small B-cell lymphomas, and to further distinguish the four main subtypes of small B-cell lymphomas. Two datasets were included: a discovery cohort (n = 100) to screen for differentially expressed miRNAs and a validation cohort (n = 282) to develop classification models. The models were evaluated for accuracy in subtype prediction. MiRNA gene set enrichment was also performed to identify differentially regulated pathways. 306 miRNAs were detected and quantified, resulting in 90-miRNA classification models from which smaller panels of miRNAs biomarkers with good accuracy were derived. Bioinformatic analysis revealed the upregulation of known and other potentially relevant signaling pathways in such lymphomas. In conclusion, this study suggests that miRNA expression profiling may serve as a promising tool to aid the diagnosis of common lymphoid lesions.
Comparison of oxidative damage in Malaysian end-stage renal disease patients with or without non-insulin-dependent diabetes mellitus

Kuppusamy UR, Indran M, Ahmad T, Wong SW, Tan SY, Mahmood AA

Clin Chim Acta, 2005 Jan;351(1-2):197-201.
PMID: 15563890 DOI: 10.1016/j.cccn.2004.09.014

BACKGROUND: Comparisons of oxidative indices and total antioxidant status between end-stage renal disease (ESRD) patients with or without diabetes is scant, especially in the Asian population.
METHOD: The assays were carried out according to known established protocols.
RESULT: The present study showed that ESRD patients with or without non-insulin-dependent diabetes mellitus (NIDDM) did not have any significant differences in antioxidant enzyme activities, advanced glycated end products (AGE), advanced oxidized protein products (AOPP) and ferric reducing ability of plasma (FRAP), indicating that hyperglycemia does not exacerbate oxidative damage in ESRD. The regulation of catalase and glutathione peroxidase is also altered in ESRD. Elevated FRAP was observed in both ESRD groups (with and without NIDDM). The dialysis process did not alter the antioxidant enzyme activities but decreased AGEs and FRAP and increased AOPP levels.
CONCLUSION: Oxidative stress is present in ESRD but this is not significantly exacerbated by hyperglycemia. The contribution of components in the pathology of renal failure towards oxidative stress exceeds that of hyperglycemia.
SELEX Modifications and Bioanalytical Techniques for Aptamer-Target Binding Characterization

Tan SY, Acquah C, Sidhu A, Ongkudon CM, Yon LS, Danquah MK

Crit Rev Anal Chem, 2016 Nov;46(6):521-37.
PMID: 26980177 DOI: 10.1080/10408347.2016.1157014

The quest to improve the detection of biomolecules and cells in health and life sciences has led to the discovery and characterization of various affinity bioprobes. Libraries of synthetic oligonucleotides (ssDNA/ssRNA) with randomized sequences are employed during Systematic Evolution of Ligands by Exponential Enrichment (SELEX) to select highly specific affinity probes called aptamers. With much focus on the generation of aptamers for a variety of target molecules, conventional SELEX protocols have been modified to develop new and improved SELEX protocols yielding highly specific and stable aptamers. Various techniques have been used to analyze the binding interactions between aptamers and their cognate molecules with associated merits and limitations. This article comprehensively reviews research advancements in the generation of aptamers, analyses physicochemical conditions affecting their binding characteristics to cellular and biomolecular targets, and discusses various field applications of aptameric binding. Biophysical techniques employed in the characterization of the molecular and binding features of aptamers to their cognate targets are also discussed.
Clinical significance of aberrant microRNAs expression in predicting disease relapse/refractoriness to treatment in diffuse large B-cell lymphoma: A meta-analysis

Ting CY, Liew SM, Price A, Gan GG, Bee-Lan Ong D, Tan SY, et al.

Crit Rev Oncol Hematol, 2019 Dec;144:102818.
PMID: 31733445 DOI: 10.1016/j.critrevonc.2019.102818

The clinical significance of aberrantly expressed microRNAs in predicting treatment response to chemotherapy in diffuse large B-cell lymphoma patients (DLBCL) remains uncertain. Feasibility of microRNA testing to predict treatment outcome was evaluated. Twenty-two types of aberrantly expressed microRNAs were associated with poor treatment response; pooled hazard ratio (HR) was 2.14 [95%CI:1.78-2.57, P
Ab-Externo Implantation of XEN Gel Stent for Refractory Steroid-Induced Glaucoma After Lamellar Keratoplasty

Tan SY, Md Din N, Mohd Khialdin S, Wan Abdul Halim WH, Tang SF

Cureus, 2021 Feb 12;13(2):e13320.
PMID: 33738163 DOI: 10.7759/cureus.13320

The hazy corneal donor-recipient interface after corneal transplant may cause difficulties when implanting the XEN gel stent via ab-interno approach. We aim to describe XEN gel stent implantation via ab-externo approach in refractory steroid-induced glaucoma after corneal lamellar keratoplasty. Under local anaesthesia, the XEN injector needle was inserted 7 mm behind the limbus with the bevel facing up, directly beneath the conjunctiva and advanced to the marked 2.5 mm scleral entry wound. The needle then pierced the sclera until the needle tip was just visible in the anterior chamber (AC). The slider was pushed until the tip of the XEN stent was seen in the AC. The needle was slowly withdrawn while still pushing the slider to complete stent deployment. Subconjunctival Mitomycin C 0.01% (30 µg/0.3 mL) was then injected posterior to the bleb. Three eyes of three patients with steroid-induced glaucoma after lamellar keratoplasty underwent XEN gel stent implantation via ab-externo approach placed at the superotemporal quadrant. Pre-operatively, all patients had uncontrolled IOP between 30-45 mmHg despite maximum medications and selective laser trabeculoplasty. After XEN gel stent implantation, IOP ranged between 10-17 mmHg with one or two topical antiglaucoma at 12 months. Complications include hypotony maculopathy, stent migration and hyphaema, all of which were successfully managed. Corneal graft remained clear at 12 months. XEN gel stent implantation via ab-externo approach is able to achieve good intraocular pressure (IOP) control without compromising cornea graft in patients with steroid-induced glaucoma after lamellar keratoplasty at 12 months.
Fulltext Orbital Tumor As First Manifestation of Metastatic Renal Cell Carcinoma

Tan SY, Bastion MC, Mohd Khialdin S

Cureus, 2021 Jul;13(7):e16275.
PMID: 34373823 DOI: 10.7759/cureus.16275

Orbital metastasis from renal cell carcinoma (RCC) is uncommon. Orbital tumor, as the first presentation of RCC, is rare as the majority of orbital metastases occur after a confirmed diagnosis of primary cancer. We report a case of the metastatic orbital tumor as the first manifestation of RCC, which presented with painless left eye proptosis for two months' duration, associated with blurring of vision and diplopia. Otherwise, the systemic review was unremarkable. Examination showed left eye non-axial proptosis with a pulsatile, multilobulated mass over the left supraorbital area extending to the left frontal region, limited ocular motility, and impaired optic nerve functions. CT of the orbit showed a mass arising from the left frontal and greater wing of the left sphenoid bone, with infiltration to the left lateral rectus, left superior oblique, and lacrimal gland. Further systemic investigation with CT thorax, abdomen, and pelvis revealed left RCC with para-aortic nodes, lungs, and bone metastases. The patient was planned for palliative care.

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