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Erythrocarpines A-E, new cytotoxic limonoids from Chisocheton erythrocarpus

Awang K, Lim CS, Mohamad K, Morita H, Hirasawa Y, Takeya K, et al.

Bioorg Med Chem, 2007 Sep 1;15(17):5997-6002.
PMID: 17576066

Five new cytotoxic limonoids, erythrocarpines A-E (1-5), were isolated from the bark of Chisocheton erythrocarpus Hiern. Chemical structures, stereochemistry, and conformation were fully elucidated and characterized by 2D NMR, MS, and computational methods.
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
Coffee consumption revealed sex differences in host endogenous metabolism and gut microbiota in healthy adults

Chong CW, Wong LC, Teh CSJ, Ismail NH, Chan PQ, Lim CS, et al.

J Food Biochem, 2020 12;44(12):e13535.
PMID: 33103260 DOI: 10.1111/jfbc.13535

Coffee is rich in antioxidant and has been shown to confer various health benefits. Here, we investigated the effect of single-dose coffee consumption in healthy human subjects. About 30 healthy volunteers were recruited and given a serving of sugar free black coffee. Urine and fecal samples were collected and analyzed. Significant changes in urinary metabolites relating to coffee, gut microbial and host energy metabolisms were observed post-coffee consumption. Clear sex differences were also observed in the urinary metabolic profiles pre- and post-coffee consumption. Sex differences in richness and composition of gut microbiota were observed, however, the effect of single-dose coffee consumption on host gut microbiota were unremarkable. These findings indicated that single-dose coffee consumption affects sex-specific host metabolic responses that relates to gut-microbe and energy metabolism. This study demonstrated the utility of systems biology tools to unravel complexity of host-diet biology and gut microbial responses. PRACTICAL APPLICATIONS: This study demonstrated that integrated systems biology approach enabled efficient extractions of host biochemical and microbial information that allows food industry to ascertain the impact of diet and longitudinal assessment of potential functional food in humans.
Fulltext Bridging the gap between advancements in the evolution of diagnosis and treatment towards better outcomes in achalasia

Chuah SK, Lim CS, Liang CM, Lu HI, Wu KL, Changchien CS, et al.

Biomed Res Int, 2019;2019:8549187.
PMID: 30881999 DOI: 10.1155/2019/8549187

Over the past few decades, there was an encouraging breakthrough in bridging the gap between advancements in the evolution of diagnosis and treatment towards a better outcome in achalasia. The purpose of this review is to provide updated knowledge on how the current evidence has bridged the gap between advancements in the evolution of diagnosis and treatment of esophageal achalasia. The advent of high-resolution manometry and standardization based on the Chicago classification has increased early recognition of the disease. These 3 clinical subtypes of achalasia can predict the outcomes of patients, and the introduction of POEM has revolutionized the choice of treatment. Previous evidence has shown that laparoscopic Heller myotomy (LHM) and anterior fundoplication were considered the most durable treatments for achalasia. Based on the current evidence, POEM has been evolving as a promising strategy and is effective against all 3 types of achalasia, but the efficacy of POEM is based on short- and medium-term outcome studies from a limited number of centers. Types I and II achalasia respond well to POEM, LHM, and PD, while most studies have shown that type III achalasia responds better to POEM than to LHM and PD. In general, among the 3 subtypes of achalasia, type II achalasia has the most favorable outcomes after medical or surgical therapies. The long-term efficacy of POEM is still unknown. The novel ENDOFLIP measures the changes in intraoperative esophagogastric junction dispensability, which enables a quantitative assessment of luminal patency and sphincter distension; however, this technology is in its infancy with little data to date supporting its intraoperative use. In the future, identifying immunomodulatory drugs and the advent of stem cell therapeutic treatments, including theoretically transplanting neuronal stem cells, may achieve a functional cure. In summary, it is important to identify the clinical subtype of achalasia to initiate target therapy for these patients.
Fulltext Semi-analytical modelling and evaluation of uniformly doped silicene nanotransistors for digital logic gates

Chuan MW, Wong KL, Riyadi MA, Hamzah A, Rusli S, Alias NE, et al.

PLoS One, 2021;16(6):e0253289.
PMID: 34125874 DOI: 10.1371/journal.pone.0253289

Silicene has attracted remarkable attention in the semiconductor research community due to its silicon (Si) nature. It is predicted as one of the most promising candidates for the next generation nanoelectronic devices. In this paper, an efficient non-iterative technique is employed to create the SPICE models for p-type and n-type uniformly doped silicene field-effect transistors (FETs). The current-voltage characteristics show that the proposed silicene FET models exhibit high on-to-off current ratio under ballistic transport. In order to obtain practical digital logic timing diagrams, a parasitic load capacitance, which is dependent on the interconnect length, is attached at the output terminal of the logic circuits. Furthermore, the key circuit performance metrics, including the propagation delay, average power, power-delay product and energy-delay product of the proposed silicene-based logic gates are extracted and benchmarked with published results. The effects of the interconnect length to the propagation delay and average power are also investigated. The results of this work further envisage the uniformly doped silicene as a promising candidate for future nanoelectronic applications.
Fulltext Device performances analysis of p-type doped silicene-based field effect transistor using SPICE-compatible model

Chuan MW, Riyadi MA, Hamzah A, Alias NE, Mohamed Sultan S, Lim CS, et al.

PLoS One, 2022;17(3):e0264483.
PMID: 35239699 DOI: 10.1371/journal.pone.0264483

Moore's Law is approaching its end as transistors are scaled down to tens or few atoms per device, researchers are actively seeking for alternative approaches to leverage more-than-Moore nanoelectronics. Substituting the channel material of a field-effect transistors (FET) with silicene is foreseen as a viable approach for future transistor applications. In this study, we proposed a SPICE-compatible model for p-type (Aluminium) uniformly doped silicene FET for digital switching applications. The performance of the proposed device is benchmarked with various low-dimensional FETs in terms of their on-to-off current ratio, subthreshold swing and drain-induced barrier lowering. The results show that the proposed p-type silicene FET is comparable to most of the selected low-dimensional FET models. With its decent performance, the proposed SPICE-compatible model should be extended to the circuit-level simulation and beyond in future work.
Correction to: Prospective observational study on Pazopanib in patients treated for advanced or metastatic renal cell carcinoma in countries in Asia Pacific, North Africa, and Middle East regions: PARACHUTE study

Erman M, Biswas B, Danchaivijitr P, Chen L, Wong YF, Hashem T, et al.

BMC Cancer, 2021 Nov 09;21(1):1191.
PMID: 34753434 DOI: 10.1186/s12885-021-08848-8
Fulltext Prospective observational study on Pazopanib in patients treated for advanced or metastatic renal cell carcinoma in countries in Asia Pacific, North Africa, and Middle East regions: PARACHUTE study

Erman M, Biswas B, Danchaivijitr P, Chen L, Wong YF, Hashem T, et al.

BMC Cancer, 2021 Sep 14;21(1):1021.
PMID: 34521387 DOI: 10.1186/s12885-021-08738-z

BACKGROUND: Clinical effectiveness and safety data of pazopanib in patients with advanced or mRCC in real-world setting from Asia Pacific, North Africa, and Middle East countries are lacking.
METHODS: PARACHUTE is a phase IV, prospective, non-interventional, observational study. Primary endpoint was the proportion of patients remaining progression free at 12 months. Secondary endpoints were ORR, PFS, safety and tolerability, and relative dose intensity (RDI).
RESULTS: Overall, 190 patients with a median age of 61 years (range: 22.0-96.0) were included. Most patients were Asian (70%), clear-cell type RCC was the most common (81%), with a favourable (9%), intermediate (47%), poor (10%), and unknown (34%) MSKCC risk score. At the end of the observational period, 78 patients completed the observational period and 112 discontinued the study; 60% of patients had the starting dose at 800 mg. Median RDI was 82%, with 52% of patients receiving 10%) TEAEs related to pazopanib included diarrhoea (30%), palmar-plantar erythrodysesthesia syndrome (15%), and hypertension (14%).
CONCLUSIONS: Results of the PARACHUTE study support the use of pazopanib in patients with advanced or mRCC who are naive to VEGF-TKI therapy. The safety profile is consistent with that previously reported by pivotal and real-world evidence studies.
Isoprenyl caffeate, a major compound in manuka propolis, is a quorum-sensing inhibitor in Chromobacterium violaceum

Gemiarto AT, Ninyio NN, Lee SW, Logis J, Fatima A, Chan EW, et al.

Antonie Van Leeuwenhoek, 2015 Aug;108(2):491-504.
PMID: 26059863 DOI: 10.1007/s10482-015-0503-6

The emergence of antibiotic-resistant bacterial pathogens, especially Gram-negative bacteria, has driven investigations into suppressing bacterial virulence via quorum sensing (QS) inhibition strategies instead of bactericidal and bacteriostatic approaches. Here, we investigated several bee products for potential compound(s) that exhibit significant QS inhibitory (QSI) properties at the phenotypic and molecular levels in Chromobacterium violaceum ATCC 12472 as a model organism. Manuka propolis produced the strongest violacein inhibition on C. violaceum lawn agar, while bee pollen had no detectable QSI activity and honey had bactericidal activity. Fractionated manuka propolis (pooled fraction 5 or PF5) exhibited the largest violacein inhibition zone (24.5 ± 2.5 mm) at 1 mg dry weight per disc. In C. violaceum liquid cultures, at least 450 µg/ml of manuka propolis PF5 completely inhibited violacein production. Gene expression studies of the vioABCDE operon, involved in violacein biosynthesis, showed significant (≥two-fold) down-regulation of vioA, vioD and vioE in response to manuka propolis PF5. A potential QSI compound identified in manuka propolis PF5 is a hydroxycinnamic acid-derivative, isoprenyl caffeate, with a [M-H] of 247. Complete violacein inhibition in C. violaceum liquid cultures was achieved with at least 50 µg/ml of commercial isoprenyl caffeate. In silico docking experiments suggest that isoprenyl caffeate may act as an inhibitor of the violacein biosynthetic pathway by acting as a competitor for the FAD-binding pockets of VioD and VioA. Further studies on these compounds are warranted toward the development of anti-pathogenic drugs as adjuvants to conventional antibiotic treatments, especially in antibiotic-resistant bacterial infections.
Fulltext Antibacterial activity of biosynthesized gold nanoparticles using biomolecules from Lignosus rhinocerotis and chitosan

Katas H, Lim CS, Nor Azlan AYH, Buang F, Mh Busra MF

Saudi Pharm J, 2019 Feb;27(2):283-292.
PMID: 30766441 DOI: 10.1016/j.jsps.2018.11.010

A simple, cost-effective, and environmentally friendly method is needed for synthesizing metal nanoparticles, including gold nanoparticles (AuNPs). In this study, AuNPs were synthesized with Lignosus rhinocerotis sclerotial extract (LRE) and chitosan (CS) as reducing and stabilizing agents, respectively. Different LRE concentrations from cold and hot water extraction (CWE and HWE, respectively) were used to reduce chloroauric acid (HAuCl4) to form AuNPs. Positively charged chitosan stabilized AuNPs (CS-AuNPs) mediated by LRE exhibited a surface plasmon resonance (SPR) band at 533 nm. The CS-AuNPs synthesized using CWE had a smaller particle size (49.5 ± 6.7-82.4 ± 28.0 nm) compared to that of the HWE samples (80.3 ± 23.4-125.3 ± 41.5 nm), depending on LRE concentration. FTIR results suggested protein and polysaccharides in LRE were the sources of reducing power, reducing gold ions to AuNPs. CS-AuNPs were mostly spherical with higher LRE concentrations, whereas some triangular, pentagonal, irregular, and rod shaped AuNPs were observed at lower LRE concentrations. CS-AuNPs mediated by LRE displayed effective antibacterial activity against gram-negative (Pseudomonas aeruginosa and Escherichia coli) and gram-positive bacteria (Staphylococcus aureus and Bacillus sp.). Thus, the biosynthesized AuNPs using LRE and chitosan provide opportunities for developing stable and eco-friendly nanoparticles with effective antibacterial properties.
A comparative study of Eldoncards for blood grouping ABO and RH0 (d) with the Tile Method of typing

Kuah KB, Lim CS

Med J Malaysia, 1974 Jun;28(4):273-5.
PMID: 4278822
Candida and invasive candidiasis: back to basics

Lim CS, Rosli R, Seow HF, Chong PP

Eur J Clin Microbiol Infect Dis, 2012 Jan;31(1):21-31.
PMID: 21544694 DOI: 10.1007/s10096-011-1273-3

The ubiquitous Candida spp. is an opportunistic fungal pathogen which, despite treatment with antifungal drugs, can cause fatal bloodstream infections (BSIs) in immunocompromised and immunodeficient persons. Thus far, several major C. albicans virulence factors have been relatively well studied, including morphology switching and secreted degradative enzymes. However, the exact mechanism of Candida pathogenesis and the host response to invasion are still not well elucidated. The relatively recent discovery of the quorum-sensing molecule farnesol and the existence of quorum sensing as a basic regulatory phenomenon of the C. albicans population behavior has revolutionized Candida research. Through population density regulation, the quorum-sensing mechanism also controls the cellular morphology of a C. albicans population in response to environmental factors, thereby, effectively placing morphology switching downstream of quorum sensing. Thus, the quorum-sensing phenomenon has been hailed as the 'missing piece' of the pathogenicity puzzle. Here, we review what is known about Candida spp. as the etiological agents of invasive candidiasis and address our current understanding of the quorum-sensing phenomenon in relation to virulence in the host.
Transcriptome profiling of endothelial cells during infections with high and low densities of C. albicans cells

Lim CS, Rosli R, Seow HF, Chong PP

Int J Med Microbiol, 2011 Aug;301(6):536-46.
PMID: 21371935 DOI: 10.1016/j.ijmm.2010.12.002

Systemic infections of Candida albicans, the most prevalent fungal pathogen in humans, are on the rise in recent years. However, the exact mode of pathogenesis of this fungus is still not well elucidated. Previous studies using C. albicans mutants locked into the yeast form via gene deletion found that this form was avirulent and did not induce significant differential expression of host genes in vitro. In this study, a high density of C. albicans was used to infect human umbilical vein endothelial cells (HUVEC), resulting in yeast-form infections, whilst a low density of C. albicans resulted in hyphae infections. Transcriptional profiling of HUVEC response to these infections showed that high densities of C. albicans induced a stronger, broader transcriptional response from HUVEC than low densities of C. albicans infection. Many of the genes that were significantly differentially expressed were involved in apoptosis and cell death. In addition, conditioned media from the high-density infections caused a significant reduction in HUVEC viability, suggesting that certain molecules released during C. albicans and HUVEC interactions were capable of causing cell death. This study has shown that C. albicans yeast-forms, at high densities, cannot be dismissed as avirulent, but instead could possibly contribute to C. albicans pathogenesis.
An alternative Candida spp. cell wall disruption method using a basic sorbitol lysis buffer and glass beads

Lim CS, Tung CH, Rosli R, Chong PP

J Microbiol Methods, 2008 Dec;75(3):576-8.
PMID: 18727938 DOI: 10.1016/j.mimet.2008.07.026

This report describes a modified, cost-effective method of cell wall disruption for the yeast Candida spp., which employs the use of glass beads in a simple sorbitol lysis buffer. This method can be used in conjunction with a commercial RNA or genomic DNA isolation method to obtain high-quality RNA or DNA.
Fulltext Risk assessment of exposure to lead in tap water among residents of Seri Kembangan, Selangor state, Malaysia

Lim CS, Shaharuddin MS, Sam WY

Glob J Health Sci, 2013 Mar;5(2):1-12.
PMID: 23445691 DOI: 10.5539/gjhs.v5n2p1

A cross sectional study was conducted to estimate risk of exposure to lead via tap water ingestion pathway for the population of Seri Kembangan (SK).
Response of exhaled nitric oxide to inhaled corticosteroids in patients with stable COPD: A systematic review and meta-analysis

Lim CS, Rani FA, Tan LE

Clin Respir J, 2018 Jan;12(1):218-226.
PMID: 27328740 DOI: 10.1111/crj.12518

INTRODUCTION: To our knowledge, no meta-analysis has investigated the response of FeNO levels to corticosteroid treatment in ex-smokers with chronic obstructive pulmonary disease (COPD).

OBJECTIVES: This meta-analysis assessed the potential role of fraction of exhaled nitric oxide (FeNO) as a biomarker for corticosteroid response in ex-smokers with stable COPD.

METHODS: Medline, Cochrane, EMBASE, Google Scholar databases were searched until November 5, 2014 using the following terms: corticosteroid, chronic obstructive pulmonary disease, COPD, nitric oxide, NO, exhaled nitric oxide. Only randomized controlled trials (RCT) or two-arm prospective studies were included. The primary outcome measure was FeNO before and after treatment with inhaled corticosteroids (ICS) in ex-smokers with COPD. Sensitivity analysis was also performed.

RESULTS: Five studies were included in the analysis with a total of 171 COPD patients. All five studies included 125 ex-smokers and two of these also included 46 current smokers. There was a significant decrease of FeNO in ex-smoking COPD patients following inhaled corticosteroid treatment (-7.51, 95% CI: -11.51 to -3.51; P =0.003); and in a population of subjects that included both smokers and ex-smokers (-1.99, 95% CI: -3.41 to -0.56; P =0.006).

CONCLUSION: Our findings indicate that FeNO levels significantly decreased with corticosteroid treatment in ex-smokers with COPD. Additional studies are required to evaluate whether concurrent smoking has significant effect on FeNO response to ICS.
2-dodecanol (decyl methyl carbinol) inhibits hyphal formation and SIR2 expression in C. albicans

Lim CS, Wong WF, Rosli R, Ng KP, Seow HF, Chong PP

J Basic Microbiol, 2009 Dec;49(6):579-83.
PMID: 19810039 DOI: 10.1002/jobm.200900035

Candida albicans is capable of undergoing yeast-hypha transition to attain pathogenicity in humans. In this study, we investigated the differential expression of CaSIR2 via quantitative real-time PCR (qPCR), during yeast-hypha transition with and without the presence of 2-dodecanol. SIR2 transcript levels were found to be significantly enhanced after hyphal induction as compared to the yeast form. This study found that 2-dodecanol is able to inhibit hyphal development and block SIR2 up-regulation, even in hyphal-inducing growth conditions. We suggest that SIR2 may be involved in Candida albicans quorum-sensing and serum-induced yeast-hyphae transition via the Ras1-cAMP-Efg1 signalling cascade.
Inclusion bodies of recombinant Epstein-Barr virus capsid antigen p18 as potential immobilized antigens in enzyme immunoassays for detection of nasopharyngeal carcinoma

Lim CS, Goh SL, Kariapper L, Krishnan G, Lim YY, Ng CC

Clin Chim Acta, 2015 Aug 25;448:206-10.
PMID: 26164385 DOI: 10.1016/j.cca.2015.07.008

Development of indirect enzyme-linked immunosorbent assays (ELISAs) often utilizes synthetic peptides or recombinant proteins from Escherichia coli as immobilized antigens. Because inclusion bodies (IBs) formed during recombinant protein expression in E. coli are commonly thought as misfolded aggregates, only refolded proteins from IBs are used to develop new or in-house diagnostic assays. However, the promising utilities of IBs as nanomaterials and immobilized enzymes as shown in recent studies have led us to explore the potential use of IBs of recombinant Epstein-Barr virus viral capsid antigen p18 (VCA p18) as immobilized antigens in ELISAs for serologic detection of nasopharyngeal carcinoma (NPC).
On optimizing the blocking step of indirect enzyme-linked immunosorbent assay for Epstein-Barr virus serology

Lim CS, Krishnan G, Sam CK, Ng CC

Clin Chim Acta, 2013 Jan 16;415:158-61.
PMID: 23043757 DOI: 10.1016/j.cca.2012.08.031

Because blocking agent occupies most binding surface of a solid phase, its ability to prevent nonspecific binding determines the signal-to-noise ratio (SNR) and reliability of an enzyme-linked immunosorbent assay (ELISA).
A Rare Combination: Dengue Fever Complicated With Guillain-Barre Syndrome

Lim CS, Kaisbain N, Lim WJ

Cureus, 2023 Jun;15(6):e40957.
PMID: 37503499 DOI: 10.7759/cureus.40957

Guillain-Barre syndrome (GBS) is an uncommon neurological complication of dengue viral infection. It is more commonly reported with Campylobacter jejuni, Epstein-Barr virus, and Cytomegalovirus infection. We report an uncommon case of a 49-year-old man with dengue fever, who developed bilateral lower limb weakness and areflexia on day two of dengue illness. He was diagnosed with GBS as a sequel of dengue infection with the nerve conduction study showing evidence of demyelinating neuropathy. He recovered gradually without immunotherapy and was discharged after a week of hospitalization.

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