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Article ; Online: Differential implications of gut-related metabolites on outcomes between heart failure and myocardial infarction.

Israr, Muhammad Zubair / Salzano, Andrea / Sarmad, Sarir / Ng, Leong L / Suzuki, Toru

European journal of preventive cardiology

2023 Volume 31, Issue 3, Page(s) 368–372

MeSH term(s)	Humans ; Heart Failure/diagnosis ; Heart Failure/therapy ; Myocardial Infarction/diagnosis
Language	English
Publishing date	2023-09-22
Publishing country	England
Document type	Journal Article
ZDB-ID	2626011-6
ISSN	2047-4881 ; 2047-4873
ISSN (online)	2047-4881
ISSN	2047-4873
DOI	10.1093/eurjpc/zwad305
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Article ; Online: Quantifying the HDL proteome by mass spectrometry: how many proteins truly associate with HDL? Reply.

Ng, Leong L / Voors, Adriaan A

European journal of heart failure

2018 Volume 20, Issue 6, Page(s) 1077–1078

MeSH term(s)	Heart Failure ; Humans ; Mass Spectrometry ; Proteome ; Proteomics
Chemical Substances	Proteome
Language	English
Publishing date	2018-03-02
Publishing country	England
Document type	Letter ; Comment
ZDB-ID	1483672-5
ISSN	1879-0844 ; 1388-9842
ISSN (online)	1879-0844
ISSN	1388-9842
DOI	10.1002/ejhf.1173
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Zs.A 5299: Show issues

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Article: Proteomics Studies in Gestational Diabetes Mellitus: A Systematic Review and Meta-Analysis.

Sriboonvorakul, Natthida / Hu, Jiamiao / Boriboonhirunsarn, Dittakarn / Ng, Leong Loke / Tan, Bee Kang

Journal of clinical medicine

2022 Volume 11, Issue 10

Abstract: Gestational Diabetes Mellitus (GDM) is the most common metabolic complication during pregnancy and is associated with serious maternal and fetal complications such as pre-eclampsia and stillbirth. Further, women with GDM have approximately 10 times ... ...

Abstract	Gestational Diabetes Mellitus (GDM) is the most common metabolic complication during pregnancy and is associated with serious maternal and fetal complications such as pre-eclampsia and stillbirth. Further, women with GDM have approximately 10 times higher risk of diabetes later in life. Children born to mothers with GDM also face a higher risk of childhood obesity and diabetes later in life. Early prediction/diagnosis of GDM leads to early interventions such as diet and lifestyle, which could mitigate the maternal and fetal complications associated with GDM. However, no biomarkers identified to date have been proven to be effective in the prediction/diagnosis of GDM. Proteomic approaches based on mass spectrometry have been applied in various fields of biomedical research to identify novel biomarkers. Although a number of proteomic studies in GDM now exist, a lack of a comprehensive and up-to-date meta-analysis makes it difficult for researchers to interpret the data in the existing literature. Thus, we undertook a systematic review and meta-analysis on proteomic studies and GDM. We searched MEDLINE, EMBASE, Web of Science and Scopus from inception to January 2022. We searched Medline, Embase, CINHAL and the Cochrane Library, which were searched from inception to February 2021. We included cohort, case-control and observational studies reporting original data investigating the development of GDM compared to a control group. Two independent reviewers selected eligible studies for meta-analysis. Data collection and analyses were performed by two independent reviewers. The PROSPERO registration number is CRD42020185951. Of 120 articles retrieved, 24 studies met the eligibility criteria, comparing a total of 1779 pregnant women (904 GDM and 875 controls). A total of 262 GDM candidate biomarkers (CBs) were identified, with 49 CBs reported in at least two studies. We found 22 highly replicable CBs that were significantly different (nine CBs were upregulated and 12 CBs downregulated) between women with GDM and controls across various proteomic platforms, sample types, blood fractions and time of blood collection and continents. We performed further analyses on blood (plasma/serum) CBs in early pregnancy (first and/or early second trimester) and included studies with more than nine samples (nine studies in total). We found that 11 CBs were significantly upregulated, and 13 CBs significantly downregulated in women with GDM compared to controls. Subsequent pathway analysis using Database for Annotation, Visualization and Integrated Discovery (DAVID) bioinformatics resources found that these CBs were most strongly linked to pathways related to complement and coagulation cascades. Our findings provide important insights and form a strong foundation for future validation studies to establish reliable biomarkers for GDM.
Language	English
Publishing date	2022-05-12
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm11102737
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Article ; Online: The Edge Effect in High-Throughput Proteomics: A Cautionary Tale.

Maxwell, Colleen B / Sandhu, Jatinderpal K / Cao, Thong H / McCann, Gerry P / Ng, Leong L / Jones, Donald J L

Journal of the American Society for Mass Spectrometry

2023 Volume 34, Issue 6, Page(s) 1065–1072

Abstract: In order for mass spectrometry to continue to grow as a platform for high-throughput clinical and translational research, careful consideration must be given to quality control by ensuring that the assay performs reproducibly and accurately and precisely. ...

Abstract	In order for mass spectrometry to continue to grow as a platform for high-throughput clinical and translational research, careful consideration must be given to quality control by ensuring that the assay performs reproducibly and accurately and precisely. In particular, the throughput required for large cohort clinical validation in biomarker discovery and diagnostic screening has driven the growth of multiplexed targeted liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) assays paired with sample preparation and analysis in multiwell plates. However, large scale MS-based proteomics studies are often plagued by batch effects: sources of technical variation in the data, which can arise from a diverse array of sources such as sample preparation batches, different reagent lots, or indeed MS signal drift. These batch effects can confound the detection of true signal differences, resulting in incorrect conclusions being drawn about significant biological effects or lack thereof. Here, we present an intraplate batch effect termed the edge effect arising from temperature gradients in multiwell plates, commonly reported in preclinical cell culture studies but not yet reported in a clinical proteomics setting. We present methods herein to ameliorate the phenomenon including proper assessment of heating techniques for multiwell plates and incorporation of surrogate standards, which can normalize for intraplate variation.
MeSH term(s)	Humans ; Chromatography, Liquid/methods ; Tandem Mass Spectrometry/methods ; Proteomics/methods ; Quality Control ; Reference Standards
Language	English
Publishing date	2023-05-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	1073671-2
ISSN	1879-1123 ; 1044-0305
ISSN (online)	1879-1123
ISSN	1044-0305
DOI	10.1021/jasms.3c00035
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Zs.A 4618: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Use of Nonhuman Sera as a Highly Cost-Effective Internal Standard for Quantitation of Multiple Human Proteins Using Species-Specific Tryptic Peptides: Applicability in Clinical LC-MS Analyses.

Williams, Geraldine / Couchman, Lewis / Taylor, David R / Sandhu, Jatinderpal K / Slingsby, Oliver C / Ng, Leong L / Moniz, Cajetan F / Jones, Donald J L / Maxwell, Colleen B

Journal of proteome research

2024

Abstract: Quantitation of proteins using liquid chromatography-tandem mass spectrometry (LC-MS/MS) is complex, with a multiplicity of options ranging from label-free techniques to chemically and metabolically labeling proteins. Increasingly, for clinically ... ...

Abstract	Quantitation of proteins using liquid chromatography-tandem mass spectrometry (LC-MS/MS) is complex, with a multiplicity of options ranging from label-free techniques to chemically and metabolically labeling proteins. Increasingly, for clinically relevant analyses, stable isotope-labeled (SIL) internal standards (ISs) represent the "gold standard" for quantitation due to their similar physiochemical properties to the analyte, wide availability, and ability to multiplex to several peptides. However, the purchase of SIL-ISs is a resource-intensive step in terms of cost and time, particularly for screening putative biomarker panels of hundreds of proteins. We demonstrate an alternative strategy utilizing nonhuman sera as the IS for quantitation of multiple human proteins. We demonstrate the effectiveness of this strategy using two high abundance clinically relevant analytes, vitamin D binding protein [Gc globulin] (DBP) and albumin (ALB). We extend this to three putative risk markers for cardiovascular disease: plasma protease C1 inhibitor (SERPING1), annexin A1 (ANXA1), and protein kinase, DNA-activated catalytic subunit (PRKDC). The results show highly specific, reproducible, and linear measurement of the proteins of interest with comparable precision and accuracy to the gold standard SIL-IS technique. This approach may not be applicable to every protein, but for many proteins it can offer a cost-effective solution to LC-MS/MS protein quantitation.
Language	English
Publishing date	2024-03-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	2078618-9
ISSN	1535-3907 ; 1535-3893
ISSN (online)	1535-3907
ISSN	1535-3893
DOI	10.1021/acs.jproteome.3c00762
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Zs.A 6189: Show issues

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Article ; Online: Distilling ethics, compassion, science and the art of medicine.

Ng, Leong / Lucire, Yolande

BMJ (Clinical research ed.)

2016 Volume 355, Page(s) i6510

MeSH term(s)	Empathy ; Ethics, Medical ; Humans ; Medicine ; Science
Language	English
Publishing date	2016-12-05
Publishing country	England
Document type	Letter
ZDB-ID	1362901-3
ISSN	1756-1833 ; 0959-8154 ; 0959-8146 ; 0959-8138 ; 0959-535X ; 1759-2151
ISSN (online)	1756-1833
ISSN	0959-8154 ; 0959-8146 ; 0959-8138 ; 0959-535X ; 1759-2151
DOI	10.1136/bmj.i6510
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Article ; Online: Endothelial dysfunction, endothelial nitric oxide bioavailability, tetrahydrobiopterin, and 5-methyltetrahydrofolate in cardiovascular disease. Where are we with therapy?

Yuyun, Matthew F / Ng, Leong L / Ng, G André

Microvascular research

2018 Volume 119, Page(s) 7–12

Abstract: Homeostasis around vascular endothelium is a function of the equilibrium between the bioavailability of nitric oxide (NO) and oxidizing reactive oxygen species (ROS). Within the vascular endothelium, NO enhances vasodilatation, reduces platelet ... ...

Abstract	Homeostasis around vascular endothelium is a function of the equilibrium between the bioavailability of nitric oxide (NO) and oxidizing reactive oxygen species (ROS). Within the vascular endothelium, NO enhances vasodilatation, reduces platelet aggression and adhesion (anti-thrombotic), prevents smooth muscle proliferation, inhibits adhesion of leukocytes and expression of pro-inflammatory cytokines genes (anti-inflammatory), and counters the oxidation of low density lipoprotein (LDL) cholesterol. A shift in the equilibrium that favours NO deficiency and ROS formation leads to endothelial dysfunction and cardiovascular disease. The synthesis of NO is catalysed by nitric oxide synthase and co-factored by tetrahydrobiopterin (BH4), nicotinamide-adenine-dinucleotide phosphate (NADPH), flavin adenine dinucleotide (FAD), and flavin mononucleotide (FMN). The focus of this review is on endothelial nitric oxide synthase (eNOS), although we recognize that the other nitric oxide synthases may contribute as well. Levels of homocysteine and the active metabolite of folate, 5-methyltetrahydrofolate (5-MTHF), play a determining role in circulating levels of nitric oxide. We review endothelial nitric oxide bioavailabilty in relation to endothelial dysfunction as well as the therapeutic strategies involving the nitric oxide synthesis pathway. Although folate supplementation improves endothelial function, results from large clinical trials and meta-analyses on palpable clinical endpoints have been inconsistent. There are however, encouraging results from animal and clinical studies of supplementation with the co-factor for nitric oxide synthesis, BH4, though its tendency to be oxidized to dihydrobiopterin (BH2) remains problematic. Understanding how to maintain a high ratio of BH4 to BH2 appears to be the key that will likely unlock the therapeutic potential of nitric oxide synthesis pathway.
MeSH term(s)	Biopterins/analogs & derivatives ; Biopterins/metabolism ; Cardiovascular Diseases/drug therapy ; Cardiovascular Diseases/metabolism ; Cardiovascular Diseases/physiopathology ; Dietary Supplements ; Endothelium, Vascular/drug effects ; Endothelium, Vascular/metabolism ; Endothelium, Vascular/physiopathology ; Folic Acid/therapeutic use ; Hemodynamics/drug effects ; Homocysteine/metabolism ; Humans ; Nitric Oxide/metabolism ; Nitric Oxide Synthase Type III/metabolism ; Oxidative Stress ; Signal Transduction ; Tetrahydrofolates/metabolism
Chemical Substances	Tetrahydrofolates ; Homocysteine (0LVT1QZ0BA) ; Biopterins ; Nitric Oxide (31C4KY9ESH) ; Folic Acid (935E97BOY8) ; NOS3 protein, human (EC 1.14.13.39) ; Nitric Oxide Synthase Type III (EC 1.14.13.39) ; sapropterin (EGX657432I) ; 5-methyltetrahydrofolate (TYK22LML8F)
Language	English
Publishing date	2018-03-27
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	80307-8
ISSN	1095-9319 ; 0026-2862
ISSN (online)	1095-9319
ISSN	0026-2862
DOI	10.1016/j.mvr.2018.03.012
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Article: Plasma desmosine for prediction of outcomes after acute myocardial infarction.

Ali, Kashan / Israr, Muhammad Zubair / Ng, Leong L / Mordi, Ify / Lang, Chim C / Kuzmanova, Elena / Huang, Jeffrey T-J / Choy, Anna-Maria

Frontiers in cardiovascular medicine

2022 Volume 9, Page(s) 992388

Abstract: Background: Elastin degradation is implicated in the pathology of vulnerable plaque. Recent studies show promising results for plasma desmosine (pDES), an elastin-specific degradation product, as a marker of cardiovascular disease (CVD) outcomes. The ... ...

Abstract	Background: Elastin degradation is implicated in the pathology of vulnerable plaque. Recent studies show promising results for plasma desmosine (pDES), an elastin-specific degradation product, as a marker of cardiovascular disease (CVD) outcomes. The aim of this study was to investigate the potential role of pDES as a marker of clinical outcome in patients with acute myocardial infarction (AMI). Materials and methods: In this case-control study, we studied 236 AMI patients: 79 patients who had death and/or myocardial infarction (MI) at 2 years, and 157 patients who did not have an event at 2 years. pDES was measured using a validated liquid chromatography-tandem mass spectrometry method. Association of pDES with adverse outcomes, and the incremental value of pDES to global registry of acute coronary events (GRACE) score for risk stratification was assessed. Results: pDES levels were elevated in patients with the composite outcome of death/MI at 2 years ( Conclusion: pDES concentrations predict clinical outcomes in patients with AMI, demonstrating its potential role as a prognostic marker in AMI.
Language	English
Publishing date	2022-11-21
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2781496-8
ISSN	2297-055X
ISSN	2297-055X
DOI	10.3389/fcvm.2022.992388
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Article ; Online: Circulating sphingolipids and relationship to cardiac remodelling before and following a low-energy diet in asymptomatic Type 2 Diabetes.

Brady, Emer M / Cao, Thong H / Moss, Alastair J / Athithan, Lavanya / Ayton, Sarah L / Redman, Emma / Argyridou, Stavroula / Graham-Brown, Matthew P M / Maxwell, Colleen B / Jones, Donald J L / Ng, Leong / Yates, Thomas / Davies, Melanie J / McCann, Gerry P / Gulsin, Gaurav S

BMC cardiovascular disorders

2024 Volume 24, Issue 1, Page(s) 25

Abstract: Background: Heart failure with preserved ejection fraction (HFpEF) is a heterogenous multi-system syndrome with limited efficacious treatment options. The prevalence of Type 2 diabetes (T2D) continues to rise and predisposes patients to HFpEF, and HFpEF ...

Abstract	Background: Heart failure with preserved ejection fraction (HFpEF) is a heterogenous multi-system syndrome with limited efficacious treatment options. The prevalence of Type 2 diabetes (T2D) continues to rise and predisposes patients to HFpEF, and HFpEF remains one of the biggest challenges in cardiovascular medicine today. Novel therapeutic targets are required to meet this important clinical need. Deep phenotyping studies including -OMIC analyses can provide important pathogenic information to aid the identification of such targets. The aims of this study were to determine; 1) the impact of a low-energy diet on plasma sphingolipid/ceramide profiles in people with T2D compared to healthy controls and, 2) if the change in sphingolipid/ceramide profile is associated with reverse cardiovascular remodelling. Methods: Post-hoc analysis of a randomised controlled trial (NCT02590822) including adults with T2D with no cardiovascular disease who completed a 12-week low-energy (∼810 kcal/day) meal-replacement plan (MRP) and matched healthy controls (HC). Echocardiography, cardiac MRI and a fasting blood for lipidomics were undertaken pre/post-intervention. Candidate biomarkers were identified from case-control comparison (fold change > 1.5 and statistical significance p < 0.05) and their response to the MRP reported. Association between change in biomarkers and change indices of cardiac remodelling were explored. Results: Twenty-four people with T2D (15 males, age 51.1 ± 5.7 years), and 25 HC (15 male, 48.3 ± 6.6 years) were included. Subjects with T2D had increased left ventricular (LV) mass:volume ratio (0.84 ± 0.13 vs. 0.70 ± 0.08, p < 0.001), increased systolic function but impaired diastolic function compared to HC. Twelve long-chain polyunsaturated sphingolipids, including four ceramides, were downregulated in subjects with T2D at baseline. Three sphingomyelin species and all ceramides were inversely associated with LV mass:volume. There was a significant increase in all species and shift towards HC following the MRP, however, none of these changes were associated with reverse cardiac remodelling. Conclusion: The lack of association between change in sphingolipids/ceramides and reverse cardiac remodelling following the MRP casts doubt on a causative role of sphingolipids/ceramides in the progression of heart failure in T2D. Trial registration: NCT02590822.
MeSH term(s)	Adult ; Female ; Humans ; Male ; Middle Aged ; Biomarkers ; Ceramides ; Diabetes Mellitus, Type 2 ; Fasting ; Heart Failure ; Sphingolipids ; Stroke Volume/physiology ; Ventricular Function, Left ; Ventricular Remodeling
Chemical Substances	Biomarkers ; Ceramides ; Sphingolipids
Language	English
Publishing date	2024-01-03
Publishing country	England
Document type	Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	2059859-2
ISSN	1471-2261 ; 1471-2261
ISSN (online)	1471-2261
ISSN	1471-2261
DOI	10.1186/s12872-023-03623-y
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Article ; Online: Association of epicardial adipose tissue with early structural and functional cardiac changes in Type 2 diabetes.

Ayton, Sarah L / Yeo, Jian L / Gulsin, Gaurav S / Dattani, Abhishek / Bilak, Joanna / Deshpande, Aparna / Arnold, J Ranjit / Singh, Anvesha / Graham-Brown, Matthew P M / Ng, Leong / Jones, Donald / Slomka, Piotr / Dey, Damini / Moss, Alastair J / Brady, Emer M / McCann, Gerry P

European journal of radiology

2024 Volume 174, Page(s) 111400

Abstract: Background: Dysregulated epicardial adipose tissue (EAT) may contribute to the development of heart failure in Type 2 diabetes (T2D). This study aimed to evaluate the associations between EAT volume and composition with imaging markers of subclinical ... ...

Abstract	Background: Dysregulated epicardial adipose tissue (EAT) may contribute to the development of heart failure in Type 2 diabetes (T2D). This study aimed to evaluate the associations between EAT volume and composition with imaging markers of subclinical cardiac dysfunction in people with T2D and no prevalent cardiovascular disease. Methods: Prospective case-control study enrolling participants with and without T2D and no known cardiovascular disease. Two hundred and fifteen people with T2D (median age 63 years, 60 % male) and thirty-nine non-diabetics (median age 59 years, 62 % male) were included. Using computed tomography (CT), total EAT volume and mean CT attenuation, as well as, low attenuation (Hounsfield unit range -190 to -90) EAT volume were quantified by a deep learning method and volumes indexed to body surface area. Associations with cardiac magnetic resonance-derived left ventricular (LV) volumes and strain indices were assessed using linear regression. Results: T2D participants had higher LV mass/volume ratio (median 0.89 g/mL [0.82-0.99] vs 0.79 g/mL [0.75-0.89]) and lower global longitudinal strain (GLS; 16.1 ± 2.3 % vs 17.2 ± 2.2 %). Total indexed EAT volume correlated inversely with mean CT attenuation. Low attenuation indexed EAT volume was 2-fold higher (18.8 cm Conclusions: Higher EAT volumes seen in T2D are associated with a lower mean CT attenuation. Low attenuation indexed EAT volume is independently, but only weakly, associated with markers of subclinical cardiac dysfunction in T2D.
MeSH term(s)	Humans ; Male ; Middle Aged ; Female ; Epicardial Adipose Tissue ; Case-Control Studies ; Diabetes Mellitus, Type 2/complications ; Pericardium/diagnostic imaging ; Adipose Tissue/diagnostic imaging ; Heart Failure ; Ventricular Dysfunction, Left/diagnostic imaging ; Ventricular Dysfunction, Left/etiology
Language	English
Publishing date	2024-02-29
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	138815-0
ISSN	1872-7727 ; 0720-048X
ISSN (online)	1872-7727
ISSN	0720-048X
DOI	10.1016/j.ejrad.2024.111400
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