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Fulltext Autophagic Degradation of Misfolded Nuclear Receptor Co-repressor (NCoR) Is Linked to the Growth of Tumor Cells in HBX Positive Hepatocellular Carcinoma (HCC)

Tan SY, Visvanathan S, Abu Hassan R, Khan M

Front Oncol, 2019;9:1335.
PMID: 31850220 DOI: 10.3389/fonc.2019.01335

Hepatitis B virus (HBV) is causally linked to hepatocellular injury and cell death, which are followed by hepatocellular carcinoma (HCC) after a long latent period. The HBV derived X protein (HBX) is the most potent carcinogenic factor for HCC, however, the molecular mechanism of HBX-induced transformation of hepatic cells in HCC is poorly understood. We have shown that nuclear receptor co-repressor (NCoR) is essential for the spatial repression of global transcription by the promyelocytic leukemia oncogenic domains (PODs), a frequent target of viral oncoproteins like HBX and that disintegration of PODs due to misfolded conformation dependent loss (MCDL) of NCoR is linked to promyelocytic and monocytic acute myeloid leukemia (AML). Given the key role of NCoR in cellular homeostasis across various tissue subtypes, we hypothesized that HBX-induced MCDL of NCoR might be linked to HCC through similar mechanism. Based on this hypothesis, the conformation of NCoR in HCC derived tumor cells and primary human tissue sections were analyzed and a selective MCDL of NCoR in HBX positive HCC cells was identified. HBX triggered the misfolding of NCoR through ubiquitination, followed by its degradation by autophagy, thus suggesting a cross talk between ubiquitin proteasome system (UPS) and autophagy lysosomal pathway (ALP) in MCDL of NCoR in HBX positive HCC cells. SiRNA-induced NCoR ablation selectively impaired the growth and survival of HBX positive HCC cells, suggesting a role of MCDL in the growth and survival of HBX positive HCC cells. These finding identify a possible crosstalk between UPS and ALP in the misfolding and loss of NCoR in HBX positive HCC cells and suggest a role of autophagic recycling of misfolded NCoR in the activation of oncogenic metabolic signaling in HCC. The misfolded NCoR reported in this study represents a novel conformation based molecular target which could be valuable in the design and development of tumor cell specific diagnostic and therapeutic approach for HBX positive HCC.
Heavy metal quantification of classroom dust in school environment and its impacts on children health from Rawang (Malaysia)

Tan SY, Praveena SM, Abidin EZ, Cheema MS

Environ Sci Pollut Res Int, 2018 Dec;25(34):34623-34635.
PMID: 30315534 DOI: 10.1007/s11356-018-3396-x

This study aimed to determine bioavailable heavy metal concentrations (As, Cd, Co, Cu, Cr, Ni, Pb, Zn) and their potential sources in classroom dust collected from children's hand palms in Rawang (Malaysia). This study also aimed to determine the association between bioavailable heavy metal concentration in classroom dust and children's respiratory symptoms. Health risk assessment (HRA) was applied to evaluate health risks (non-carcinogenic and carcinogenic) due to heavy metals in classroom dust. The mean of bioavailable heavy metal concentrations in classroom dust found on children's hand palms was shown in the following order: Zn (1.25E + 01 μg/g) > Cu (9.59E-01 μg/g) > Ni (5.34E-01 μg/g) > Cr (4.72E-02 μg/g) > Co (2.34E-02 μg/g) > As (1.77E-02 μg/g) > Cd (9.60E-03 μg/g) > Pb (5.00E-03 μg/g). Hierarchical cluster analysis has clustered 17 sampling locations into three clusters, whereby cluster 1 (S3, S4, S6, S15) located in residential areas and near to roads exposed to vehicle emissions, cluster 2 (S10, S12, S9, S7) located near Rawang town and cluster 3 (S13, S16, S1, S2, S8, S14, S11, S17, S5) located near industrial, residential and plantation areas. Emissions from vehicles, plantations and industrial activities were found as the main sources of heavy metals in classroom dust in Rawang. There is no association found between bioavailable heavy metal concentrations and respiratory symptoms, except for Cu (OR = 0.03). Health risks (non-carcinogenic and carcinogenic risks) indicated that there are no potential non-carcinogenic and carcinogenic risks of heavy metals in classroom dust toward children health.
Prevalence of falls among community-dwelling elderly and its associated factors: A cross-sectional study in Perak, Malaysia

Yeong UY, Tan SY, Yap JF, Choo WY

Malays Fam Physician, 2016;11(1):7-14.
PMID: 28461842 MyJurnal

INTRODUCTION: Fall is a major cause of injuries and can increase the risk of early mortality among elderly. The objective of this study was to determine the prevalence of falls among community-dwelling elderly in rural Malaysia and its associated factors.
METHODS: Data were obtained from a cross-sectional survey in five randomly selected districts in the state of Perak, Malaysia. A total of 250 households were randomly selected. A total of 811 individuals aged 60 years or more were recruited and interviewed using a structured questionnaire. Information about socio-demographic, history of falls in the past 1 year, medical history, drug history and physical activity level were enquired.
RESULTS: The prevalence of falls in the past 1 year among community-dwelling elderly was reported to be 4.07%. Indigenous elderly (Adjusted odd ratio, AOR = 6.06, 95% CI = 1.10-33.55, p = 0.039) and living alone (AOR = 2.60, 95% CI = 1.04-6.50, p = 0.042) were shown to be factors associated with falls. Physical activity level, number of co-morbidities and number of medications used were not associated with falls.
CONCLUSION: Elderly of indigenous ethnicity and living alone are the main factors associated with falls in this population. Indigenous people may be at higher risk, which warrant further investigation with a larger sample to improve the precision of estimates.
Appraising the performance of oil palm fibre biochar for low concentration ammoniacal nitrogen recovery from aquaculture wastewater

Ahmad T, Sethupathi S, Bashir MJK, Tan SY

Environ Technol, 2022 Dec 12.
PMID: 36428222 DOI: 10.1080/09593330.2022.2152735

Oil palm fibre is a type of solid waste generated from palm oil processing plant. At present, there is no proper utilization of this abundant waste. Ammoniacal nitrogen (NH3-N) has received a lot of attention as a water pollutant due to its toxicity, which has an impact on both the environment and human health. In aquaculture wastewater (AQW), NH3-N is present in low concentrations (<10 ppm), and removing low concentrations of NH3-N is tedious. Thus, this study focuses on the potential of oil palm fibre biochar (OPFB) for sustainable low concentration NH3-N recovery from AQW and the recovered spent adsorbent to be used as a bio-fertilizer. The Physico-chemical properties of OPFB show a positive correlation with NH3-N recovery. A significant reduction of value-added metals in OPFB has confirmed the recovery of NH3-N through the ion exchange process. The adsorption isotherms and kinetics of NH3-N recovery had good correlation coefficients under the Freundlich and pseudo-second-order kinetic model confirming a multilayer heterogeneous and chemical adsorption respectively. Thermodynamic parameters indicated that the recovery process via adsorption was exothermic and had a Physio-chemical mechanism. At optimum conditions, OPFB could recover up to 66% of NH3-N actual AQW. The properties of spent OPFB showed potential reutilization as a soil amendment agent or biofertilizer which could be easily degraded.
Fulltext Outcomes of Renal Transplantation in Brunei Darussalam over a Twenty-Year Period (1993-2012)

Tan J, Khalil MA, Tan SY, Khalil M, Ahmed D, Zinna S, et al.

J Transplant, 2014;2014:784805.
PMID: 25478205 DOI: 10.1155/2014/784805

Objectives. Brunei Darussalam has a high prevalence and incidence of end stage renal disease (ESRD). Up until 2012, all renal transplantations were performed in overseas centres, either as government-sponsored (living-related transplantation) or as self-sponsored (commercialized transplantation) ones. We hypothesize that graft and patient survival of Brunei renal transplant patients are on a par with international standards. Materials and Methods. Data of all renal transplant patients in Brunei were analysed over a twenty-year period from registry records and case notes. Comparative survival data from other countries were obtained from PubMed-listed literature. Results. A total of 49 transplantation procedures were performed in foreign centres between 1993 and 2012. 29 were government-sponsored and 20 were self-sponsored transplantations. The 5- and 10-year overall patient survival rates were 93.3% and 90.1%, respectively. The 5- and 10-year overall graft survival rates were 91.1% and 81.2%. There is no difference in the survival outcomes of government-sponsored and self-sponsored patients. Living-related (government-sponsored) and commercialised (self-sponsored) grafts had equivalent survival to those reported in the literature. Conclusion. Our survival data was on par with those achieved in many countries. We hope to use this information to convince local stakeholders and patients to favour transplantation as the preferred modality of RRT.
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.
Nutritional status and dietary intake of children with acute leukaemia during induction or consolidation chemotherapy

Tan SY, Poh BK, Nadrah MH, Jannah NA, Rahman J, Ismail MN

J Hum Nutr Diet, 2013 Jul;26 Suppl 1:23-33.
PMID: 23701375 DOI: 10.1111/jhn.12074

The assessment of nutritional status among paediatric patients is important for the planning and execution of nutritional strategies that strive to optimise the quality of life and growth among sick children. The present study aimed to evaluate the nutritional status and dietary intake among children with acute leukaemia.
Grossly delayed graft function in a living related kidney transplant recipient: a case report

Thye YL, Lim SK, Wong CM, Keng TC, Chong YB, Tan SY

Transplant Proc, 2008 Sep;40(7):2435-6.
PMID: 18790259 DOI: 10.1016/j.transproceed.2008.07.051

Delayed graft function is a potentially challenging problem especially in cadaveric kidney transplant recipients. It adversely impacts long-term graft survival. It is rarely seen in living kidney transplants. Recovery of graft function usually occurs within a month. The chances of recovery of graft function diminish with further prolongation of delayed function. In fact, recovery of graft function after 3 months has rarely been described, we report herein recovery of graft function after 132 days of nonfunction in a living related kidney transplant.
A study of association of the complement C4 mutations with systemic lupus erythematosus in the Malaysian population

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

Lupus, 2007;16(9):750-4.
PMID: 17728371 DOI: 10.1177/0961203307079454

The aim of the present study was to investigate the association of C4 gene mutations with systemic lupus erythematosus, in 130 Malaysian SLE patients and 130 healthy controls. Generally, various PCR approaches were used to screen the mutations of the C4 genes, which included 2 bp (+TC) insertions at codon 1213 in exon 29, 1 bp deletions (-C) at codon 811 in exon 20, 1 bp (-C), 2 bp (-GT) deletions at codons 522 and 497 in exon 13 and null alleles. No mutations located at exons 13, 20 and 29 of the C4 gene, were detected amongst the patient and control samples in this study. C4A*Q0 was found in two out of the 130 control samples, while C4B*Q0 was present in two out of the 130 SLE patients. Overall, our results do not demonstrate a significant association to these known C4 mutations identified by previous studies, in the Malaysian scenario.
A follow-up study on the effects of a milk supplement on bone mineral density of postmenopausal Chinese women in Malaysia

Ting GP, Tan SY, Chan SP, Karuthan C, Zaitun Y, Suriah AR, et al.

J Nutr Health Aging, 2007 Jan-Feb;11(1):69-73.
PMID: 17315084

A previous study on a randomized controlled trial in 173 postmenopausal Chinese women in Kuala Lumpur showed that milk supplementation was effective to reduce bone loss at the total body, lumbar spine, femoral neck and total hip compared to the control group on a usual diet (Chee et al. 2003).
The influence of CYP3A gene polymorphisms on cyclosporine dose requirement in renal allograft recipients

Eng HS, Mohamed Z, Calne R, Lang CC, Mohd MA, Seet WT, et al.

Kidney Int, 2006 May;69(10):1858-64.
PMID: 16612333

Cyclosporine is a substrate of cytochrome P-450 3A (CYP3A) subfamily of enzymes and characterized by a narrow therapeutic range with wide interindividual variation in pharmacokinetics. A few single-nucleotide polymorphisms detected in CYP3A genes have been shown to correlate significantly with the CYP3A protein expression and activity. We therefore postulated that these polymorphisms could be responsible for some of the interindividual variation in cyclosporine pharmacokinetics. The objective of our study is to determine correlation if any between single-nucleotide polymorphisms of CYP3A5 and CYP3AP1 on cyclosporine dose requirement and concentration-to-dose ratio in renal allograft recipients. Cyclosporine-dependent renal allograft recipients were genotyped for CYP3A5 A6986G and CYP3AP1 G-44A. The cyclosporine dosages prescribed and the corresponding cyclosporine trough levels for each patient were recorded so that cyclosporine dose per weight (mg/kg/day) and concentration-to-dose ratio (C(0)/D, whereby C(0) is trough level and D is daily dose per weight) could be calculated. A total of 67 patients were recruited for our study. The dose requirement for 1, 3, and 6 months post-transplantation ranged 2.3-11.4, 1.0-9.0, and 1.4-7.2 mg/kg/day, respectively. Patients with *1*1*1*1 (n=5) CYP3A5- and CYP3AP1-linked genotypes needed higher dose of cyclosporine compared to patients with *1*3*1*3 (n = 27) and *3*3*3*3 (n = 33) linked genotypes in months 3 and 6 post-transplantation (P < 0.016). The identification of patients with *1*1*1*1 by CYP3A5 and CYP3AP1 genotyping may have a clinically significant and positive impact on patient outcome with reduced rejection rate by providing pretransplant pharmacogenetic information for optimization of cyclosporine A dosing.
Posttransplant lymphoproliferative disease masquerading as postbiopsy hematoma

Gan WH, Thye YL, Chang SH, Chua CB, Looi LM, Tan SY

Transplant Proc, 2004 Sep;36(7):2148-9.
PMID: 15518779
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.
Disseminated nocardiosis with bilateral intraocular involvement in a renal allograft patient

Tan SY, Tan LH, Teo SM, Thiruventhiran T, Kamarulzaman A, Hoh HB

Transplant Proc, 2000 Nov;32(7):1965-6.
PMID: 11120022
Cyclosporine-associated encephalopathy: a case report and literature review

Chang SH, Lim CS, Low TS, Chong HT, Tan SY

Transplant Proc, 2001 12 26;33(7-8):3700-1.
PMID: 11750577
Cadaveric organ donation at University Hospital Kuala Lumpur

Chen TP, Teo SM, Tan JC, Koh SN, Ambalavanar N, Tan SY

Transplant Proc, 2000 Nov;32(7):1809-10.
PMID: 11119946
Acute renal failure following multiple wasp stings

Thiruventhiran T, Goh BL, Leong CL, Cheah PL, Looi LM, Tan SY

Nephrol Dial Transplant, 1999 Jan;14(1):214-7.
PMID: 10052513
Fulltext Peritoneal implantation of ureter in a cadaveric kidney transplant recipient

Tan SY, Lim CS, Teo SM, Lee SH, Razack A, Loh CS

Med J Malaysia, 2003 Dec;58(5):769-70.
PMID: 15190667

We report here a case of a kidney transplant recipient in whom the ureter was initially implanted into the peritoneum. Excessive ultrafiltration volume and reversal of serum vs dialysate creatinine ratio when the patient was recommenced on continuous ambulatory peritoneal dialysis first suggested the diagnosis which was subsequently confirmed by a plain abdominal x-ray demonstrating placement of ureteric stent in the peritoneum. This rare complication was successfully corrected with surgical re-implantation of ureter into the bladder and 5 years later, the patient remains well with good graft function.
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.
Diel osmorespiration rhythms of juvenile marble goby (Oxyeleotris marmorata)

Lim LS, Tan SY, Tuzan AD, Kawamura G, Mustafa S, Rahmah S, et al.

Fish Physiol Biochem, 2020 Aug;46(4):1621-1629.
PMID: 32430644 DOI: 10.1007/s10695-020-00817-5

Oxyeleotris marmorata is an ambush predator. It is known for slow growth rate and high market demand. Farming of O. marmorata still remains a challenge. In order to establish a proper feeding practice to stimulate growth, knowledge of its metabolic processes and cost should be examined. Therefore, this study was designed to investigate the diel osmorespiration rhythms of O. marmorata in response to feeding challenge by using an osmorespirometry assay. The results have shown that oxygen consumption rate of the fed fish was approximately 3 times higher than that of the unfed fish in early evening to support specific dynamic action. Digestion and ingestion processes were likely to be completed within 18-20 h in parallel with the ammonia excretion noticeable in early morning. Under resting metabolism, metabolic oxygen consumption was influenced by diel phase, but no effect was noted in ammonia excretion. As a nocturnal species, O. marmorata exhibited standard aerobic metabolic mode under dark phase followed by light phase, with high oxygen consumption rate found in either fed or unfed fish. It can be confirmed that both the diel phase and feeding have a significant interactive impact on oxygen consumption rate, whereas ammonia metabolism is impacted by feeding state. High metabolic rate of O. marmorata supports the nocturnal foraging activity in this fish. This finding suggested that feeding of O. marmorata should be performed during nighttime and water renewal should be conducted during daytime.

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