Felicia Au

University of Ottawa

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Renaud Vincent

Health Canada

James Gomes

University of Ottawa

Ajoy Basak

University of Ottawa

Sabit Cakmak

Health Canada

Premkumari Kumarathasan

Health Canada

Prem Kumarathasan

Government of Canada

William D. Fraser

Université de Sherbrooke

Mandy Fisher

Health Canada

Tye E. Arbuckle

Health Canada

Erica Blais

Health Canada

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Health Canada

University of Ottawa

Carleton University

McGill University

Government of Canada

Instituto Butantan

Analytical Services

Natural Sciences and Engineering Research Council

Université de Montréal

Ottawa Hospital

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Maternal Biomarkers Relevant to Pregnancy and Birth Outcomes

ISEE Conference Abstracts (2018)

James Gomes Felicia Au Ajoy Basak Renaud Vincent Prem Kumarathasan

Background: There is a need to elucidate specific mechanisms in-utero during pregnancy and to delineate the role of the biological markers. The expression of biological markers could help in understanding the effect of environmental exposures on pregnancy outcomes.This study aims to examine the role of biological biomarkers and the underlying mechanisms that may be associated with infant birth weights, gestational age and infant development in-utero. Methods: Electronic searches were conducted in relevant databases and all relevant papers were retrieved. Studies were selected if they evaluated maternal blood plasma/serum biomarkers proposed to influence adverse birth outcomes in the neonate. Data was extracted and odds ratios from each study and meta-analysis was conducted. Results: A total of 54 studies (35 for meta-analysis), including 43,702 women and collectively 50 biomarkers, were included in this study. The fixed effect point estimates for inflammation- related biomarkers were, 0.845(95%CI: 0.829-0.861, p<0.0001 for adverse birth outcomes and for hormone and growth factor-related biomarkers were 0.55(95%CI: 0.551-0.577, p=0.0013) for adverse birth outcomes. Pooled risk estimates for inflammation- related, hormone and growth factor-related biomarkers for preterm births were 0.845(95%CI:0.829-0.861, p<0.0001) and 0.554(95%CI: 0.531-0.578, p<0.0001) respectively. Comparable risk estimates for delivery between 30 weeks and 37 weeks were 0.967(95%CI: 0.951-0.985, p<0.0001) and 0.759(95%CI: 0.759(0.657-0.861, p<0.0001) for inflammation related- and hormone and growth factor related- biomarkers respectively. Significant associations were seen between biomarkers and adverse birth outcomes with no apparent publication bias. Conclusions: The two subsets of plasma markers identified in this study (inflammation-related and growth factor/hormone-related) may serve as valuable tools in the investigation of maternal molecular mechanisms modulating adverse birth outcomes.

Premature birth

10.1289/isesisee.2018.p02.3220

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Blood metal levels and third trimester maternal plasma matrix metalloproteinases (MMPs)

Chemosphere (2016)

Felicia Au A Bielecki Erica Blais Mandy Fisher Sabit Cakmak

10.1016/j.chemosphere.2016.06.011

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Characterization of a New Hypotensive Peptide from the Venom of Snake bothrops jararaca (Bj)

Current Proteomics (2023)

Ajoy Basak Eurı́dice Carmona Felicia Au Rosa A.M.B. Borgheresi

Background: Snake venom has become a key source of many bioactive peptides, enzymes, and toxins associated with blood coagulation and neuronal toxicity. In the past, a number of bradykinin potentiating peptides have been isolated from snake venom that display hypotensive activity due to their inhibitory action towards Angiotensin-Converting Enzyme (ACE). Significant interest has developed to isolate, characterize, and subsequently design peptide analogs as potent ACE-inhibitors which may find therapeutic applications for the treatment of hypertension and associated diseases. Aim: The aim of this study is to search for new bioactive peptide/s in the venom of the snake Bothrops Jararaca (Bj). Objective: The objective is to isolate and characterize new hypotensive peptides from BJ venom. Methods: We examined the venom of Bj which is known to host a range of bioactive peptides. We have isolated a new peptide (BJ-1) which displayed in vitro potent hypotensive activity. The peptide was purified via Sephadex G25 column chromatography and RP-HPLC. It was characterized by mass spectrometry, amino acid analysis, N-terminal sequencing, and chemical synthesis. Result: The peptide was identified as an octa-decapeptide with amino acid sequence as DCPSDWSSYEGHCYKPFS where the two Cys residues are likely present in free state, although they can form an internal S-S bond upon oxidation. It was fully confirmed by comparing with synthetic peptide prepared by solid phase chemistry. Both have the same molecular mass (2,108 Da) and identical bioactivity. Furthermore, we rationalize that BJ-1 may be derived from precursor protein “Coagulation factor IX/factor X binding protein (CF-IX/X-BP)” by proteolytic cleavage at the Nterminus of its B-chain within the sequence KPFS18↓E19PKN. This cleavage site contains the recognition motif of enzyme PCSK8 (Proprotein Convertase Subtilisin Kexin8) also known as Subtilisin Kexin Isozyme 1 (SKI-1) or Site 1 Protease (S1P). Despite this observation, using a synthetic peptide encompassing the proposed cleavage site and recombinant PCSK8 enzyme, we found that the enzyme responsible for generation of BJ-1 is not PCSK8. Further studies will be needed to identify the associated enzyme and fully characterize the pharmacological and biological properties of the peptide. Conclusion: Our study revealed the presence of a novel hypotensive octa-decapeptide in the venom of the snake Bothrops jararaca. It is likely derived from the A-chain of protein CF-IX/X-BP via proteolytic cleavage at the N-terminus by a protease yet to be characterized.

Bothrops jararaca

Sephadex

Bothrops

Molecular mass

10.2174/0115701646254996231130050528

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Characterization of Maternal Mechanisms Relevant to Metal Exposure-Mediated Infant Birth Weight Outcomes in the MIREC Study

ISEE Conference Abstracts (2018)

Premkumari Kumarathasan Erica Blais Felicia Au James Gomes Sanjoy K. Sinha

There is growing evidence on the association between prenatal metal exposures and adverse pregnancy outcomes. Heavy metals such as arsenic (As), cadmium (Cd), mercury (Hg) and lead (Pb) are considered as endocrine disrupting chemicals and elevated exposure to these metals during pregnancy is associated with adverse effects on maternal and infant health. Nevertheless, mechanistic understanding is required to establish biological plausibility of such associations. The objective of this study was to gain insight into metal exposure-related adverse birth outcomes by understanding maternal systemic changes at the molecular level.The Maternal-Infant Research on Environmental Chemicals (MIREC) study was employed for this purpose. Third trimester maternal plasma samples were analysed for target oxidative /nitrative stress markers (e.g 8-isoprostane, 3-nitrotyrosine) by competitive enzyme immunoassay and HPLC-Coularray as well as matrix metalloproteinases, a class of enzymes and other markers of inflammation (e.g. Cytokines, cellular adhesion molecules) were measured by affinity-based multiplex array and HPLC-Fluorescence detection methods. Pearson product moment correlations, chi-squared tests and multivariate models were used to analyse the associations among maternal blood metal (Cd, Hg, Pb, As, manganese Mn) levels, plasma biomarkers, physiological changes and birth weight. Our results revealed maternal metal exposure-specific responses (p<0.05) on markers of oxidative stress pathways (e.g 8-isoprostane) and matrix metalloproteinases (MMPs), in maternal circulation. Interestingly, statistically significant (p<0.05) correlations were seen between oxidative stress pathways, MMPs and other inflammatory mediators relevant to infant birth weight changes. Our findings imply that metal exposures potentially can mediate maternal oxidative stress pathways which can alter MMP profiles and associated inflammatory processes, thus adversely impacting on infant birth weights.

10.1289/isesisee.2018.o03.02.12

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Dementia pugilistica (DP) and Boxing Related Cranial Injuries

Felicia Au Heather Ritchie Alberto Lee

Source

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The Impact of Environmental Heavy Metal Exposures on Pregnancy and Birth Outcomes

Felicia Au

10.20381/ruor-516

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Maternal blood biomarkers and adverse pregnancy outcomes: a systematic review and meta-analysis

Critical Reviews in Toxicology (2019)

James Gomes Felicia Au Ajoy Basak Sabit Cakmak Renaud Vincent

Background: Pregnancy is a vulnerable period for the mother and the infant and exposures to environmental chemicals in utero can influence neonatal morbidity and mortality. There is a momentum toward understanding and exploring the current maternal biological mechanisms specific to in utero effects, to improve birth outcomes. This study aims to examine the current understanding of the role of biomarkers that may be associated with term of pregnancy, infant birth weights and infant development in utero.Methods: Electronic searches were conducted in PubMed, Embase, OvidMD, and Scopus databases; and all relevant research articles in English were retrieved. Studies were selected if they evaluated maternal blood plasma/serum biomarkers proposed to influence adverse birth outcomes in the neonate. Data were extracted on characteristics, quality, and odds ratios from each study and meta-analysis was conducted.Results: A total of 54 studies (35 for meta-analysis), including 43,702 women, 50 plasma markers and six descriptors of birth outcomes were included in the present study. The random effect point estimates for risk of adverse birth outcomes were 1.61(95%CI: 1.39–1.85, p < 0.0001) for inflammation-related biomarkers and 1.65(95%CI: 1.22–2.25, p = 0.0013) for growth factor/hormone-related biomarkers. All subgroups of plasma markers showed significant associations with adverse birth outcomes with no apparent study bias.Conclusions: The two subsets of plasma markers identified in this study (inflammation-related and growth factor/hormone-related) may serve as potentially valuable tools in the investigation of maternal molecular mechanisms, especially select pathways underlying inflammatory and immunological mediation in terms of modulating adverse infant outcomes. Future large, prospective cohort studies are needed to validate the promising plasma biomarkers, and to examine other maternal biological matrices such as cervicovaginal fluid and urine.

10.1080/10408444.2019.1629873

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Citations (36)