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Fulltext Asperuloside Enhances Taste Perception and Prevents Weight Gain in High-Fat Fed Mice

Ishaq M, Tran D, Wu Y, Nowak K, Deans BJ, Xin JTZ, et al.

Front Endocrinol (Lausanne), 2021;12:615446.
PMID: 33927690 DOI: 10.3389/fendo.2021.615446

Asperuloside is an iridoid glycoside found in many medicinal plants that has produced promising anti-obesity results in animal models. In previous studies, three months of asperuloside administration reduced food intake, body weight, and adipose masses in rats consuming a high fat diet (HFD). However, the mechanisms by which asperuloside exerts its anti-obesity properties were not clarified. Here, we investigated homeostatic and nutrient-sensing mechanisms regulating food intake in mice consuming HFD. We confirmed the anti-obesity properties of asperuloside and, importantly, we identified some mechanisms that could be responsible for its therapeutic effect. Asperuloside reduced body weight and food intake in mice consuming HFD by 10.5 and 12.8% respectively, with no effect on mice eating a standard chow diet. Fasting glucose and plasma insulin were also significantly reduced. Mechanistically, asperuloside significantly reduced hypothalamic mRNA ghrelin, leptin, and pro-opiomelanocortin in mice consuming HFD. The expression of fat lingual receptors (CD36, FFAR1-4), CB1R and sweet lingual receptors (TAS1R2-3) was increased almost 2-fold by the administration of asperuloside. Our findings suggest that asperuloside might exert its therapeutic effects by altering nutrient-sensing receptors in the oral cavity as well as hypothalamic receptors involved in food intake when mice are exposed to obesogenic diets. This signaling pathway is known to influence the subtle hypothalamic equilibrium between energy homeostasis and reward-induced overeating responses. The present pre-clinical study demonstrated that targeting the gustatory system through asperuloside administration could represent a promising and effective new anti-obesity strategy.
Fulltext Delayed surgery for localised and metastatic renal cell carcinoma: a systematic review and meta-analysis for the COVID-19 pandemic

Chan VW, Tan WS, Leow JJ, Tan WP, Ong WLK, Chiu PK, et al.

World J Urol, 2021 Dec;39(12):4295-4303.
PMID: 34031748 DOI: 10.1007/s00345-021-03734-1

PURPOSE: The COVID-19 pandemic has led to the cancellation or deferment of many elective cancer surgeries. We performed a systematic review on the oncological effects of delayed surgery for patients with localised or metastatic renal cell carcinoma (RCC) in the targeted therapy (TT) era.
METHOD: The protocol of this review is registered on PROSPERO(CRD42020190882). A comprehensive literature search was performed on Medline, Embase and Cochrane CENTRAL using MeSH terms and keywords for randomised controlled trials and observational studies on the topic. Risks of biases were assessed using the Cochrane RoB tool and the Newcastle-Ottawa Scale. For localised RCC, immediate surgery [including partial nephrectomy (PN) and radical nephrectomy (RN)] and delayed surgery [including active surveillance (AS) and delayed intervention (DI)] were compared. For metastatic RCC, upfront versus deferred cytoreductive nephrectomy (CN) were compared.
RESULTS: Eleven studies were included for quantitative analysis. Delayed surgery was significantly associated with worse cancer-specific survival (HR 1.67, 95% CI 1.23-2.27, p
Fulltext 2021 Asian Pacific Society of Cardiology Consensus Recommendations on the Use of P2Y12 Receptor Antagonists in the Asia-Pacific Region: Special Populations

Tan JWC, Chew DP, Tsui KL, Tan D, Duplyakov D, Hammoudeh A, et al.

Eur Cardiol, 2021 Feb;16:e43.
PMID: 34815751 DOI: 10.15420/ecr.2021.35

Advanced age, diabetes, and chronic kidney disease not only increase the risk for ischaemic events in chronic coronary syndromes (CCS) but also confer a high bleeding risk during antiplatelet therapy. These special populations may warrant modification of therapy, especially among Asians, who have displayed characteristics that are clinically distinct from Western patients. Previous guidance has been provided regarding the classification of high-risk CCS and the use of newer-generation P2Y12 inhibitors (i.e. ticagrelor and prasugrel) after acute coronary syndromes (ACS) in Asia. The authors summarise evidence on the use of these P2Y12 inhibitors during the transition from ACS to CCS and among special populations. Specifically, they present recommendations on the roles of standard dual antiplatelet therapy, shortened dual antiplatelet therapy and single antiplatelet therapy among patients with coronary artery disease, who are either transitioning from ACS to CCS; elderly; or with chronic kidney disease, diabetes, multivessel coronary artery disease and bleeding events during therapy.
Asian Pacific Society of Cardiology Consensus Recommendations on Dyslipidaemia

Koh N, Ference BA, Nicholls SJ, Navar AM, Chew DP, Kostner K, et al.

Eur Cardiol, 2021 Feb;16:e54.
PMID: 35024056 DOI: 10.15420/ecr.2021.36

The prevalence of dyslipidaemia has been increasing in the Asia-Pacific region and this is attributed to dietary changes and decreasing physical activity. While there has been substantial progress in dyslipidaemia therapy, its management in the region is hindered by limitations in awareness, adherence and healthcare costs. The Asian Pacific Society of Cardiology (APSC) developed these consensus recommendations to address the need for a unified approach to managing dyslipidaemia. These recommendations are intended to guide general cardiologists and internists in the assessment and treatment of dyslipidaemia and are hoped to pave the way for improving screening, early diagnosis and treatment. The APSC expert panel reviewed and appraised the evidence using the Grading of Recommendations Assessment, Development, and Evaluation system. Consensus recommendations were developed, which were then put to an online vote. The resulting consensus recommendations tackle contemporary issues in the management of dyslipidaemia, familial hypercholesterolaemia and lipoprotein(a) in the Asia-Pacific region.
Development of a Malaysian potentially inappropriate prescribing screening tool in older adults (MALPIP): a Delphi study

Chang CT, Chan HK, Cheah WK, Tan MP, Ch'ng ASH, Thiam CN, et al.

J Pharm Policy Pract, 2023 Oct 19;16(1):122.
PMID: 37858273 DOI: 10.1186/s40545-023-00630-4

INTRODUCTION: Polypharmacy and potentially inappropriate medications (PIM) are common among older adults. To guide appropriate prescribing, healthcare professionals often rely on explicit criteria to identify and deprescribe inappropriate medications, or to start medications due to prescribing omission. However, most explicit PIM criteria were developed with inadequate guidance from quality metrics or integrating real-world data, which are rich and valuable data source.
AIM: To develop a list of medications to facilitate appropriate prescribing among older adults.
METHODS: A preliminary list of PIM and potential prescribing omission (PPO) were generated from systematic review, supplemented with local pharmacovigilance data of adverse reaction incidents among older people. Twenty-one experts from nine specialties participated in two Delphi to determine the list of PIM and PPO in February and March 2023. Items that did not reach consensus after the second Delphi round were adjudicated by six geriatricians.
RESULTS: The preliminary list included 406 potential candidates, categorised into three sections: PIM independent of diseases, disease dependent PIM and omitted drugs that could be restarted. At the end of Delphi, 92 items were decided as PIM, including medication classes, such as antacids, laxatives, antithrombotics, antihypertensives, hormones, analgesics, antipsychotics, antidepressants, and antihistamines. Forty-two disease-specific PIM criteria were included, covering circulatory system, nervous system, gastrointestinal system, genitourinary system, and respiratory system. Consensus to start potentially omitted treatment was achieved in 35 statements across nine domains.
CONCLUSIONS: The newly developed PIM criteria can serve as a useful tool to guide clinicians and pharmacists in identifying PIMs and PPOs during medication review and facilitating informed decision-making for appropriate prescribing.
Fulltext Severe Pediatric Adenovirus 7 Disease in Singapore Linked to Recent Outbreaks across Asia

Ng OT, Thoon KC, Chua HY, Tan NW, Chong CY, Tee NW, et al.

Emerg Infect Dis, 2015 Jul;21(7):1192-6.
PMID: 26079293 DOI: 10.3201/eid2107.141443

During November 2012-July 2013, a marked increase of adenovirus type 7 (Ad7) infections associated with severe disease was documented among pediatric patients in Singapore. Phylogenetic analysis revealed close genetic links with severe Ad7 outbreaks in China, Taiwan, and other parts of Asia.
Fulltext Validation and utilization of an internally controlled multiplex Real-time RT-PCR assay for simultaneous detection of enteroviruses and enterovirus A71 associated with hand foot and mouth disease

Thanh TT, Anh NT, Tham NT, Van HM, Sabanathan S, Qui PT, et al.

Virol J, 2015 Jun 09;12:85.
PMID: 26050791 DOI: 10.1186/s12985-015-0316-2

BACKGROUND: Hand foot and mouth disease (HFMD) is a disease of public health importance across the Asia-Pacific region. The disease is caused by enteroviruses (EVs), in particular enterovirus A71 (EV-A71). In EV-A71-associated HFMD, the infection is sometimes associated with severe manifestations including neurological involvement and fatal outcome. The availability of a robust diagnostic assay to distinguish EV-A71 from other EVs is important for patient management and outbreak response.
METHODS: We developed and validated an internally controlled one-step single-tube real-time RT-PCR in terms of sensitivity, linearity, precision, and specificity for simultaneous detection of EVs and EV-A71. Subsequently, the assay was then applied on throat and rectal swabs sampled from 434 HFMD patients.
RESULTS: The assay was evaluated using both plasmid DNA and viral RNA and has shown to be reproducible with a maximum assay variation of 4.41 % and sensitive with a limit of detection less than 10 copies of target template per reaction, while cross-reactivity with other EV serotypes was not observed. When compared against a published VP1 nested RT-PCR using 112 diagnostic throat and rectal swabs from 112 children with a clinical diagnosis of HFMD during 2014, the multiplex assay had a higher sensitivity and 100 % concordance with sequencing results which showed EVs in 77/112 (68.8 %) and EV-A71 in 7/112 (6.3 %). When applied to clinical diagnostics for 322 children, the assay detected EVs in throat swabs of 257/322 (79.8 %) of which EV-A71 was detected in 36/322 (11.2 %) children. The detection rate increased to 93.5 % (301/322) and 13.4 % (43/322) for EVs and EV-A71, respectively, when rectal swabs from 65 throat-negative children were further analyzed.
CONCLUSION: We have successfully developed and validated a sensitive internally controlled multiplex assay for rapid detection of EVs and EV-A71, which is useful for clinical management and outbreak control of HFMD.
Fulltext A generic assay for whole-genome amplification and deep sequencing of enterovirus A71

Tan le V, Tuyen NT, Thanh TT, Ngan TT, Van HM, Sabanathan S, et al.

J Virol Methods, 2015 Apr;215-216:30-6.
PMID: 25704598 DOI: 10.1016/j.jviromet.2015.02.011

Enterovirus A71 (EV-A71) has emerged as the most important cause of large outbreaks of severe and sometimes fatal hand, foot and mouth disease (HFMD) across the Asia-Pacific region. EV-A71 outbreaks have been associated with (sub)genogroup switches, sometimes accompanied by recombination events. Understanding EV-A71 population dynamics is therefore essential for understanding this emerging infection, and may provide pivotal information for vaccine development. Despite the public health burden of EV-A71, relatively few EV-A71 complete-genome sequences are available for analysis and from limited geographical localities. The availability of an efficient procedure for whole-genome sequencing would stimulate effort to generate more viral sequence data. Herein, we report for the first time the development of a next-generation sequencing based protocol for whole-genome sequencing of EV-A71 directly from clinical specimens. We were able to sequence viruses of subgenogroup C4 and B5, while RNA from culture materials of diverse EV-A71 subgenogroups belonging to both genogroup B and C was successfully amplified. The nature of intra-host genetic diversity was explored in 22 clinical samples, revealing 107 positions carrying minor variants (ranging from 0 to 15 variants per sample). Our analysis of EV-A71 strains sampled in 2013 showed that they all belonged to subgenogroup B5, representing the first report of this subgenogroup in Vietnam. In conclusion, we have successfully developed a high-throughput next-generation sequencing-based assay for whole-genome sequencing of EV-A71 from clinical samples.
Blood gene signature for early hepatocellular carcinoma detection in patients with chronic hepatitis B

Omar H, Lim CR, Chao S, Lee MM, Bong CW, Ooi EJ, et al.

J Clin Gastroenterol, 2015 Feb;49(2):150-7.
PMID: 25569223 DOI: 10.1097/MCG.0000000000000112

Up to 25% of chronic hepatitis B (CHB) patients eventually develop hepatocellular carcinoma (HCC), a disease with poor prognosis unless detected early. This study identifies a blood-based RNA biomarker panel for early HCC detection in CHB.
Fulltext Analysis of non-synonymous-coding variants of Parkinson's disease-related pathogenic and susceptibility genes in East Asian populations

Foo JN, Tan LC, Liany H, Koh TH, Irwan ID, Ng YY, et al.

Hum Mol Genet, 2014 Jul 15;23(14):3891-7.
PMID: 24565865 DOI: 10.1093/hmg/ddu086

To evaluate the contribution of non-synonymous-coding variants of known familial and genome-wide association studies (GWAS)-linked genes for Parkinson's disease (PD) to PD risk in the East Asian population, we sequenced all the coding exons of 39 PD-related disease genes and evaluated the accumulation of rare non-synonymous-coding variants in 375 early-onset PD cases and 399 controls. We also genotyped 782 non-synonymous-coding variants of these genes in 710 late-onset PD cases and 9046 population controls. Significant enrichment of LRRK2 variants was observed in both early- and late-onset PD (odds ratio = 1.58; 95% confidence interval = 1.29-1.93; P = 8.05 × 10(-6)). Moderate enrichment was also observed in FGF20, MCCC1, GBA and ITGA8. Half of the rare variants anticipated to cause loss of function of these genes were present in healthy controls. Overall, non-synonymous-coding variants of known familial and GWAS-linked genes appear to make a limited contribution to PD risk, suggesting that clinical sequencing of these genes will provide limited information for risk prediction and molecular diagnosis.
Self-Reported Delayed Adverse Events and Flare Following COVID-19 Vaccination Among Patients With Autoimmune Rheumatic Disease (AIRD) in Malaysia: Results From the COVAD-2 Study

Shaharir SS, Nawi AM, Mariamutu TN, Kamaruzaman L, Said MSM, Rajalingham S, et al.

Int J Rheum Dis, 2025 Jan;28(1):e70043.
PMID: 39791506 DOI: 10.1111/1756-185X.70043

OBJECTIVES: To determine the prevalence of self-reported delayed adverse events (DAEs), major AEs, and flares following COVID-19 vaccinations among patients with autoimmune rheumatic diseases (AIRDs) in Malaysia.
METHODOLOGY: An electronically validated survey from the COVID-19 vaccination in autoimmune diseases (COVAD) study group was distributed in July 2021 to patients with autoimmune diseases and healthy controls (HCs). The survey collected data on DAEs (any AE that persisted or occurred after 7 days of vaccination), any early or delayed major adverse events (MAEs), and flares following COVID-19 vaccination. Generalized estimating equation (GEE) models were performed to determine the factors associated with repeated events of DAEs, MAEs, and flares.
RESULTS: A total of 556 vaccines were administered to 204 subjects (150 AIRDs and 54 HCs), with 72.1% completing 3 doses. In multivariate GEE analysis, there was a greater frequency of minor DAEs among AIRDs versus HCs (OR 5.65, p = 0.052). The occurrence of MAEs was higher in AIRDs versus HCs (4.9% vs. 1.3%, p = 0.052), but it was no longer significant in the GEE model. In the AIRDs group, the BNT162b2 vaccine increased the risk for minor DAEs (OR4.68, p = 0.02) while patients with autoimmune multimorbidity showed a greater risk for MAEs (OR 8.25, p = 0.007). The rate of flare was 10.6% and multivariate GEE analysis revealed that The rate of flare was 10.6% and multivariate GEE analysis revealed that systemic lupus erythematosus (SLE) (OR0.31, p = 0.03) and hydroxychloroquine (HCQ) (OR 0.16, p
Lasing strategy and its influence on 30-day operative outcomes in flexible ureteroscopy with FANS: inferences from a real-world prospective multicenter study by EAU-endourology and AUSET

Gauhar V, Giulioni C, Falsetti F, Cafarelli A, Yuen SK, Fong KY, et al.

World J Urol, 2025 Oct 28;43(1):633.
PMID: 41148343 DOI: 10.1007/s00345-025-06012-6

PURPOSE: To compare operative and 30-day outcomes of dusting versus popcorning lithotripsy during flexible ureteroscopy (FURS) with flexible suction ureteral access sheaths (FANS) in a real-world multicenter study.
METHODS: This prospective analysis included 704 adults from 21 centers undergoing FURS for kidney stone with FANS between August 2023 and August 2024. Patients were stratified by lasing strategy into dusting (n = 281) or popcorning (n = 423). Operative parameters, complications, and stone-free status (SFS) at 30 days-assessed by 2 mm slice non-contrast CT scan were compared. Multivariable logistic regression identified predictors of complete clearance (no fragment).
RESULTS: Patients in the popcorning group presented with larger and denser stones (> 2 cm: 20.7% vs. 10.7%, p = 0.007; median HU 1100 vs. 1051, p = 0.003). Operative times were consistently longer with popcorning, including lasing (17 vs. 14 min), ureteroscopy (34 vs. 30 min), and overall duration (50 vs. 44 min, all p
Diagnosis and treatment of MYH9-RD in an Australasian cohort with thrombocytopenia

Rabbolini DJ, Chun Y, Latimer M, Kunishima S, Fixter K, Valecha B, et al.

Platelets, 2018 Dec;29(8):793-800.
PMID: 29090586 DOI: 10.1080/09537104.2017.1356920

MYH9-related disorders (MYH9-RDs) caused by mutation of the MYH9 gene which encodes non-muscle myosin heavy-chain-IIA (NMMHC-IIA), an important motor protein in hemopoietic cells, are the most commonly encountered cause of inherited macrothrombocytopenia. Despite distinguishing features including an autosomal dominant mode of inheritance, giant platelets on the peripheral blood film accompanied by leucocytes with cytoplasmic inclusion bodies (döhle-like bodies), these disorders remain generally under-recognized and often misdiagnosed as immune thrombocytopenia (ITP). This may result in inappropriate treatment with corticosteroids, immunosupressants and in some cases, splenectomy. We explored the efficacy of next generation sequencing (NGS) with a candidate gene panel to establish the aetiology of thrombocytopenia for individuals who had been referred to our center from hematologists in the Australasian region in whom the cause of thrombocytopenia was suspected to be secondary to an inherited condition but which remained uncharacterized despite phenotypic investigations. Pathogenic MYH9 variants were detected in 15 (15/121, 12.4%) individuals and the pathogenecity of a novel variant of uncertain significance was confirmed in a further two related individuals following immunofluorescence (IF) staining performed in our laboratory. Concerningly, only one (1/17) individual diagnosed with MYH9-RD had been referred with this as a presumptive diagnosis, in all other cases (16/17, 94.1%), a diagnosis was not suspected by referring clinicians, indicating a lack of awareness or a failing of our diagnostic approach to these conditions. We examined the mean platelet diameter (MPD) measurements as a means to better identify and quantify platelet size. MPDs in cases with MYH9-RDs were significantly larger than controls (p < 0.001) and in 91% were greater than a previously suggested threshold for platelets in cases of ITP. In addition, we undertook IF staining in a proportion of cases and confirm that this test and/or NGS are satisfactory diagnostic tests. We propose that fewer cases of MYH9-RDs would be missed if diagnostic algorithms prioritized IF and/or NGS in cases of thrombocytopenia associated with giant platelets, even if döhle-like bodies are not appreciated on the peripheral blood film. Finally, our report describes the long-term use of a thrombopoietin agonist in a case of MYH9-RD that had previously been diagnosed as ITP, and demonstrates that treatment with these agents may be possible, and is well tolerated, in this group of patients.
Fulltext Comparison of the Microbiological Quality and Safety between Conventional and Organic Vegetables Sold in Malaysia

Kuan CH, Rukayadi Y, Ahmad SH, Wan Mohamed Radzi CWJ, Thung TY, Premarathne JMKJK, et al.

Front Microbiol, 2017;8:1433.
PMID: 28824567 DOI: 10.3389/fmicb.2017.01433

Given the remarkable increase of public interest in organic food products, it is indeed critical to evaluate the microbiological risk associated with consumption of fresh organic produce. Organic farming practices including the use of animal manures may increase the risk of microbiological contamination as manure can act as a vehicle for transmission of foodborne pathogens. This study aimed to determine and compare the microbiological status between organic and conventional fresh produce at the retail level in Malaysia. A total of 152 organic and conventional vegetables were purchased at retail markets in Malaysia. Samples were analyzed for mesophilic aerobic bacteria, yeasts and molds, and total coliforms using conventional microbiological methods. Combination methods of most probable number-multiplex polymerase chain reaction (MPN-mPCR) were used to detect and quantify foodborne pathogens, including Escherichia coli O157:H7, Shiga toxin-producing E. coli (STEC), Listeria monocytogenes, Salmonella Typhimurium, and Salmonella Enteritidis. Results indicated that most types of organic and conventional vegetables possessed similar microbial count (P > 0.05) of mesophilic aerobic bacteria, yeasts and molds, and total coliforms. E. coli O157:H7 and S. Typhimurium were not detected in any sample analyzed in this study. Among the 152 samples tested, only the conventional lettuce and organic carrot were tested positive for STEC and S. Enteritidis, respectively. L. monocytogenes were more frequently detected in both organic (9.1%) and conventional vegetables (2.7%) as compared to E. coli O157:H7, S. Typhimurium, and S. Enteritidis. Overall, no trend was shown that either organically or conventionally grown vegetables have posed greater microbiological risks. These findings indicated that one particular type of farming practices would not affect the microbiological profiles of fresh produce. Therefore, regardless of farming methods, all vegetables should be subjected to appropriate post-harvest handling practices from farm to fork to ensure the quality and safety of the fresh produce.
Real-world clinical experience of biological disease modifying anti-rheumatic drugs in Malaysia rheumatoid arthritis patients

Tan BE, Lim AL, Kan SL, Lim CH, Tsang EEL, Ch'ng SS, et al.

Rheumatol Int, 2017 Oct;37(10):1719-1725.
PMID: 28695274 DOI: 10.1007/s00296-017-3772-8

The effect of biologic disease modifying anti-rheumatic drugs (bDMARDs) in treating rheumatoid arthritis (RA) in real-world clinical practice remains unknown in Southeast Asia. We aimed to assess the efficacy and safety of bDMARDs among Malaysian RA patients treated in routine clinical practice. A retrospective medical chart review of RA patients from 11 government hospitals were conducted from January 2003 to January 2014. A standardized questionnaire was used to abstract patient's demographic, clinical and treatment data. Level of disease activity was measured by DAS28 collected at baseline, 3, 6 and 12 months. Three hundred and one patients were available for analysis, mean age 41 (SD, 10.8) years, mean RA duration 12.3 (SD, 6.9) years and 98% had history of two or more conventional-synthetic DMARDs. There were 467 bDMARD courses prescribed with mean bDMARDs duration use of 12.9 months (SD 14.7). Tumour necrosis factor alpha inhibitors were the most common prescribed bDMARDs (77.1%), followed by Tocilizumab (14.6%) and Rituximab (8.4%). We observed significant improvement in mean DAS28 values from baseline to 3, 6 and 12 months (p
Fulltext Strict tropism for CD71+/CD234+ human reticulocytes limits the zoonotic potential of Plasmodium cynomolgi

Kosaisavee V, Suwanarusk R, Chua ACY, Kyle DE, Malleret B, Zhang R, et al.

Blood, 2017 09 14;130(11):1357-1363.
PMID: 28698207 DOI: 10.1182/blood-2017-02-764787

Two malaria parasites of Southeast Asian macaques, Plasmodium knowlesi and P cynomolgi, can infect humans experimentally. In Malaysia, where both species are common, zoonotic knowlesi malaria has recently become dominant, and cases are recorded throughout the region. By contrast, to date, only a single case of naturally acquired P cynomolgi has been found in humans. In this study, we show that whereas P cynomolgi merozoites invade monkey red blood cells indiscriminately in vitro, in humans, they are restricted to reticulocytes expressing both transferrin receptor 1 (Trf1 or CD71) and the Duffy antigen/chemokine receptor (DARC or CD234). This likely contributes to the paucity of detectable zoonotic cynomolgi malaria. We further describe postinvasion morphologic and rheologic alterations in P cynomolgi-infected human reticulocytes that are strikingly similar to those observed for P vivax These observations stress the value of P cynomolgi as a model in the development of blood stage vaccines against vivax malaria.
Fulltext CD24, CD44 and EpCAM enrich for tumour-initiating cells in a newly established patient-derived xenograft of nasopharyngeal carcinoma

Hoe SLL, Tan LP, Abdul Aziz N, Liew K, Teow SY, Abdul Razak FR, et al.

Sci Rep, 2017 09 28;7(1):12372.
PMID: 28959019 DOI: 10.1038/s41598-017-12045-8

Subpopulations of nasopharyngeal carcinoma (NPC) contain cells with differential tumourigenic properties. Our study evaluates the tumourigenic potential of CD24, CD44, EpCAM and combination of EpCAM/CD44 cells in NPC. CD44br and EpCAMbr cells enriched for higher S-phase cell content, faster-growing tumourigenic cells leading to tumours with larger volume and higher mitotic figures. Although CD44br and EpCAMbr cells significantly enriched for tumour-initiating cells (TICs), all cells could retain self-renewal property for at least four generations. Compared to CD44 marker alone, EpCAM/CD44dbr marker did not enhance for cells with faster-growing ability or higher TIC frequency. Cells expressing high CD44 or EpCAM had lower KLF4 and p21 in NPC subpopulations. KLF4-overexpressed EpCAMbr cells had slower growth while Kenpaullone inhibition of KLF4 transcription increased in vitro cell proliferation. Compared to non-NPC, NPC specimens had increased expression of EPCAM, of which tumours from advanced stage of NPC had higher expression. Together, our study provides evidence that EpCAM is a potentially important marker in NPC.
Association of CYP2C19*2 polymorphism with clopidogrel response and 1-year major adverse cardiovascular events in a multiethnic population with drug-eluting stents

Tan SSN, Fong AYY, Mejin M, Gerunsin J, Kong KL, Chin FYY, et al.

Pharmacogenomics, 2017 08;18(13):1225-1239.
PMID: 28745576 DOI: 10.2217/pgs-2017-0078

BACKGROUND: Patients undergoing elective percutaneous coronary intervention (PCI) with drug-eluting stents (DES) who have impaired clopidogrel response, have a higher risk of subsequent major adverse cardiovascular events (MACE).
AIM OF THE STUDY: To establish the relationship between CYP2C19 genotype, clopidogrel responsiveness and 1-year MACE.
MATERIALS & METHODS: Aspirin/clopidogrel responses were assessed with Multiplate Analyzer and CYP2C19*2 allele by SpartanRx.
RESULTS: A total of 42.0% carried ≥1 CYP2C19*2 allele. Prevalences of aspirin and clopidogrel high on-treatment platelet reactivity (HPR; local cutoffs: 300 AU*min for aspirin and 600 AU*min for clopidogrel) were 11.5% and 19.8% respectively. In multivariate ana-lysis, clopidogrel HPR was found to be an independent predictor for 1-year MACE (adj HR: 3.48, p = 0.022 ).
CONCLUSION: Having clopidogrel HPR could be a potentially modifiable risk factor guided by phenotyping.
The draft genome of tropical fruit durian (Durio zibethinus)

Teh BT, Lim K, Yong CH, Ng CCY, Rao SR, Rajasegaran V, et al.

Nat Genet, 2017 Nov;49(11):1633-1641.
PMID: 28991254 DOI: 10.1038/ng.3972

Durian (Durio zibethinus) is a Southeast Asian tropical plant known for its hefty, spine-covered fruit and sulfury and onion-like odor. Here we present a draft genome assembly of D. zibethinus, representing the third plant genus in the Malvales order and first in the Helicteroideae subfamily to be sequenced. Single-molecule sequencing and chromosome contact maps enabled assembly of the highly heterozygous durian genome at chromosome-scale resolution. Transcriptomic analysis showed upregulation of sulfur-, ethylene-, and lipid-related pathways in durian fruits. We observed paleopolyploidization events shared by durian and cotton and durian-specific gene expansions in MGL (methionine γ-lyase), associated with production of volatile sulfur compounds (VSCs). MGL and the ethylene-related gene ACS (aminocyclopropane-1-carboxylic acid synthase) were upregulated in fruits concomitantly with their downstream metabolites (VSCs and ethylene), suggesting a potential association between ethylene biosynthesis and methionine regeneration via the Yang cycle. The durian genome provides a resource for tropical fruit biology and agronomy.
Aldosterone-Producing Adenomas: Histopathology-Genotype Correlation and Identification of a Novel CACNA1D Mutation

Tan GC, Negro G, Pinggera A, Tizen Laim NMS, Mohamed Rose I, Ceral J, et al.

Hypertension, 2017 07;70(1):129-136.
PMID: 28584016 DOI: 10.1161/HYPERTENSIONAHA.117.09057

Mutations in KCNJ5, ATP1A1, ATP2B3, CACNA1D, and CTNNB1 are thought to cause the excessive autonomous aldosterone secretion of aldosterone-producing adenomas (APAs). The histopathology of KCNJ5 mutant APAs, the most common and largest, has been thoroughly investigated and shown to have a zona fasciculata-like composition. This study aims to characterize the histopathologic spectrum of the other genotypes and document the proliferation rate of the different sized APAs. Adrenals from 39 primary aldosteronism patients were immunohistochemically stained for CYP11B2 to confirm diagnosis of an APA. Twenty-eight adenomas had sufficient material for further analysis and were target sequenced at hot spots in the 5 causal genes. Ten adenomas had a KCNJ5 mutation (35.7%), 7 adenomas had an ATP1A1 mutation (25%), and 4 adenomas had a CACNA1D mutation (14.3%). One novel mutation in exon 28 of CACNA1D (V1153G) was identified. The mutation caused a hyperpolarizing shift of the voltage-dependent activation and inactivation and slowed the channel's inactivation kinetics. Immunohistochemical stainings of CYP17A1 as a zona fasciculata cell marker and Ki67 as a proliferation marker were used. KCNJ5 mutant adenomas showed a strong expression of CYP17A1, whereas ATP1A1/CACNA1D mutant adenomas had a predominantly negative expression (P value =1.20×10-4). ATP1A1/CACNA1D mutant adenomas had twice the nuclei with intense staining of Ki67 than KCNJ5 mutant adenomas (0.7% [0.5%-1.9%] versus 0.4% [0.3%-0.7%]; P value =0.04). Further, 3 adenomas with either an ATP1A1 mutation or a CACNA1D mutation had >30% nuclei with moderate Ki67 staining. In summary, similar to KCNJ5 mutant APAs, ATP1A1 and CACNA1D mutant adenomas have a seemingly specific histopathologic phenotype.

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