Kristine McGrath
University of Technology Sydney, Life Sciences, Faculty Member
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Recent reports show air pollutant magnetite nanoparticles (MNPs) in the brains of people with Alzheimer's disease (AD). Considering various field applications of MNPs because of developments in nanotechnology, the aim of this study is to... more
Recent reports show air pollutant magnetite nanoparticles (MNPs) in the brains of people with Alzheimer's disease (AD). Considering various field applications of MNPs because of developments in nanotechnology, the aim of this study is to identify major trends and data gaps in research on magnetite to allow for relevant environmental and health risk assessment. Herein, a bibliometric and systematic analysis of the published magnetite literature (n = 31 567) between 1990 to 2020 is completed. Following appraisal, publications (n = 244) are grouped into four time periods with the main research theme identified for each as 1990–1997 “oxides,” 1998–2005 “ferric oxide,” 2006–2013 “pathology,” and 2014–2020 “animal model.” Magnetite formation and catalytic activity dominate the first two time periods, with the last two focusing on the exploitation of nanoparticle engineering. Japan and China have the highest number of citations for articles published. Longitudinal analysis indicates that magnetite research for the past 30 years shifted from environmental and industrial applications, to biomedical and its potential toxic effects. Therefore, whilst this study presents the research profile of different countries, the development in research on MNPs, it also reveals that further studies on the effects of MNPs on human health is much needed.
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This chapter reviews the physiopathology of atherosclerosis and cardiovascular disease. The role of inflammatory processes, endothelium integrity and nitric oxide on atherosclerosis is presented, and the relationship between inflammation... more
This chapter reviews the physiopathology of atherosclerosis and cardiovascular disease. The role of inflammatory processes, endothelium integrity and nitric oxide on atherosclerosis is presented, and the relationship between inflammation and biomarkers of atherosclerosis is examined. The impact of exercise and nutrition on inflammation and atherosclerosis is discussed.
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AimsThe aim of this scoping review is to evaluate the current biomarkers used in the assessment of adverse cardiac remodelling in people with diabetes mellitus (DM) and in the diagnosis and prognosis of subsequent cardiovascular disease.... more
AimsThe aim of this scoping review is to evaluate the current biomarkers used in the assessment of adverse cardiac remodelling in people with diabetes mellitus (DM) and in the diagnosis and prognosis of subsequent cardiovascular disease. We aim to discuss the biomarkers' pathophysiological roles as a reflection of the cardiac remodelling mechanisms in the presence of DM.MethodsWe performed the literature search to include studies from 2003 to 2021 using the following databases: MEDLINE, Scopus, Web of Science, PubMed, and Cochrane library. Articles that met our inclusion criteria were screened and appraised before being included in this review. The PRISMA guidelines for Scoping Reviews were followed.ResultsOur literature search identified a total of 43 eligible articles, which were included in this scoping review. We identified 15 different biomarkers, each described by at least two studies, that were used to determine signs of cardiac remodelling in cardiovascular disease (CVD)...
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Cardiovascular disease (CVD) is a leading cause of mortality worldwide, with cigarette smoking being a major preventable risk factor. Smoking cessation can be difficult due to the addictive nature of nicotine and the withdrawal symptoms... more
Cardiovascular disease (CVD) is a leading cause of mortality worldwide, with cigarette smoking being a major preventable risk factor. Smoking cessation can be difficult due to the addictive nature of nicotine and the withdrawal symptoms following cessation. Electronic cigarettes (e-Cigs) have emerged as an alternative smoking cessation device, which has been increasingly used by non-smokers; however, the cardiovascular effects surrounding the use of e-Cigs remains unclear. This study aimed to investigate the effects of e-Cig aerosol condensate (EAC) (0mg and 18mg nicotine) in-vitro on human coronary artery endothelial cells (HCAEC) and in-vivo on the cardiovascular system using a mouse model of ‘e-vaping’. The results show a decrease in cell viability of HCAEC when exposed to EAC either directly or after exposure to conditioned lung cell media (p < 0.005). Reactive oxygen species and ICAM-1 expression were increased in HCAEC when exposed to EAC directly (p < 0.0005). ICAM-1 mR...
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The purpose of this study is to evaluate the literature for research trends on cerium oxide from 1990 to 2020 and identify gaps in knowledge in the emerging application(s) of CeONP. Bibliometric methods were used to identify themes in... more
The purpose of this study is to evaluate the literature for research trends on cerium oxide from 1990 to 2020 and identify gaps in knowledge in the emerging application(s) of CeONP. Bibliometric methods were used to identify themes in database searches from PubMed, Scopus and Web of Science Core Collection using SWIFT-Review, VOSviewer and SciMAT software programs. A systematic review was completed on published cerium oxide literature extracted from the Scopus database (n = 17,115), identifying themes relevant to its industrial, environmental and biomedical applications. A total of 172 publications were included in the systematic analysis and categorized into four time periods with research themes identified; “doping additives” (n = 5, 1990–1997), “catalysts” (n = 32, 1998–2005), “reactive oxygen species” (n = 66, 2006–2013) and “pathology” (n = 69, 2014–2020). China and the USA showed the highest number of citations and publications for cerium oxide research from 1990 to 2020. Long...
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Preeclampsia is a pregnancy-specific cardiovascular disorder and a leading cause of morbidity and mortality in pregnancy. Although inappropriate placental development and growth are recognized as root causes of preeclampsia, pathogenic... more
Preeclampsia is a pregnancy-specific cardiovascular disorder and a leading cause of morbidity and mortality in pregnancy. Although inappropriate placental development and growth are recognized as root causes of preeclampsia, pathogenic mechanisms are poorly understood due to limited models of the disease, particularly in early pregnancy. Here, we first confirm the aberrant expression of important vascular and inflammatory proteins, FK506-binding protein like (FKBPL) and galectin-3 (Gal-3), in human plasma and placental tissue from women with/without preeclampsia. We then employ a 3D microfluidic placental model incorporating human umbilical vein endothelial cells (HUVECs) and a first trimester trophoblast cell line (ACH-3P) to investigate FKBPL and Gal-3 signalling in inflammatory conditions. In human samples, both circulating (n = 17 controls; n = 30 preeclampsia) and placental (n ≥ 6) FKBPL and Gal-3 levels were increased in preeclampsia compared to heathy controls (plasma: FKBPL,...
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<b>Supplementary Figure 1: </b>Dynamic Light Scattering of RALA- sFlt1-e15a (red) and RALA-hFlt1 (blue) at N:P 10 with a PDI less than 0.6.
<b>Supplementary Figure 2:</b> Differential expression of FKBPL in trophoblast cell lines. 5x10<sup>5</sup> cells were seeded and incubated at 37°C in a humidified atmosphere in the presence of 5%... more
<b>Supplementary Figure 2:</b> Differential expression of FKBPL in trophoblast cell lines. 5x10<sup>5</sup> cells were seeded and incubated at 37°C in a humidified atmosphere in the presence of 5% CO<sub>2</sub> for 24 h before protein lysates were collected and western blotting performed. Data points are mean ± SEM; n=3; one-way ANOVA with Tukey's post-hoc test. <em></em>
Additional file 1: Additional Figure 1. Relative mRNA expression levels of endothelial dysfunction markers Icam1 and Vcam1 in RUPP hearts. Total RNA was collected from 30-50mg sections of cryopreserved rat hearts by a TRIsure reagent... more
Additional file 1: Additional Figure 1. Relative mRNA expression levels of endothelial dysfunction markers Icam1 and Vcam1 in RUPP hearts. Total RNA was collected from 30-50mg sections of cryopreserved rat hearts by a TRIsure reagent protocol. The relative levels of (A) Icam1 and (B) Vcam1 mRNA were quantified by real-time polymerase chain reaction (RT-PCR) adjusted to β-actin. Data presented as mean fold change ± SEM; n=7; unpaired t-test. Additional Figure 2. Relative mRNA expression levels of endothelial dysfunction markers Icam1 and Vcam1 in RUPP placentae. Total RNA was collected from 30-50mg sections of cryopreserved rat hearts by a TRIsure reagent protocol. The relative levels of (A) Icam1 and (B) Vcam1 mRNA were quantified by real-time polymerase chain reaction (RT-PCR) adjusted to β-actin. Data presented as mean fold change ± SEM; n=7; unpaired t-test. Additional Figure 3. Cell size and count of RUPP livers and F4/80 quantification by IHC. Formalin-fixed, paraffin-embedded ...
Maternal obesity imposes significant health risks in the offspring including diabetes and dyslipidemia. We previously showed that the hypoglycaemic agent exendin-4 (Ex-4) administered from weaning can reverse the maternal impact of... more
Maternal obesity imposes significant health risks in the offspring including diabetes and dyslipidemia. We previously showed that the hypoglycaemic agent exendin-4 (Ex-4) administered from weaning can reverse the maternal impact of 'transmitted disorders' in such offspring. However daily injection for six-weeks was required and the beneficial effect may lapse upon drug withdrawal. This study aimed to investigate whether short term Ex-4 treatment during suckling period in a rodent model can reverse transmitted metabolic disorders due to maternal obesity. Maternal obesity was induced in female Sprague Dawley rats by high-fat diet feeding for 6 weeks, throughout gestation and lactation. Female offspring were treated with Ex-4 (5μg/kg/day) between postnatal day (P) 4 and 14. Female offspring were harvested at weaning (P20). Lipid and glucose metabolic markers were measured in the liver and fat. Appetite regulators were measured in the plasma and hypothalamus. Maternal obesity si...
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High-fat diet (HFD)-induced comorbid cognitive and behavioural impairments are thought to be the result of persistent low-grade neuroinflammation. Metformin, a first-line medication for the treatment of type-2 diabetes, seems to... more
High-fat diet (HFD)-induced comorbid cognitive and behavioural impairments are thought to be the result of persistent low-grade neuroinflammation. Metformin, a first-line medication for the treatment of type-2 diabetes, seems to ameliorate these comorbidities, but the underlying mechanism(s) are not clear. Pituitary adenylate cyclase-activating peptide (PACAP) and vasoactive intestinal peptide (VIP) are neuroprotective peptides endowed with anti-inflammatory properties. Alterations to the PACAP/VIP system could be pivotal during the development of HFD-induced neuroinflammation. To unveil the pathogenic mechanisms underlying HFD-induced neuroinflammation and assess metformin’s therapeutic activities, (1) we determined if HFD-induced proinflammatory activity was present in vulnerable brain regions associated with the development of comorbid behaviors, (2) investigated if the PACAP/VIP system is altered by HFD, and (3) assessed if metformin rescues such diet-induced neurochemical alter...
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BACKGROUND Preeclampsia is a dangerous cardiovascular disorder of pregnancy that leads to an increased risk of future cardiovascular and metabolic disorders. Much of the pathogenesis and mechanisms involved in cardiac health in... more
BACKGROUND Preeclampsia is a dangerous cardiovascular disorder of pregnancy that leads to an increased risk of future cardiovascular and metabolic disorders. Much of the pathogenesis and mechanisms involved in cardiac health in preeclampsia are unknown. A novel anti-angiogenic protein, FKBPL, is emerging as having a potential role in both preeclampsia and cardiovascular disease (CVD). Therefore, in this study we aimed to characterise cardiac health and FKBPL regulation in the rat reduced uterine perfusion pressure (RUPP) and a 3D cardiac spheroid model of preeclampsia. METHODS The RUPP model was induced in pregnant rats and histological analysis performed on the heart, kidney, liver and placenta (n ≥ 6). Picrosirius red staining was performed to quantify collagen I and III deposition in rat hearts, placentae and livers as an indicator of fibrosis. RT-qPCR was used to determine changes in Fkbpl, Icam1, Vcam1, Flt1 and Vegfa mRNA in hearts and/or placentae and ELISA to evaluate cardia...
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Background There are a growing number of publications that report an absence of inflammatory based disease among populations that are endemic to parasitic worms (helminths) demonstrating the ability of these parasites to potentially... more
Background There are a growing number of publications that report an absence of inflammatory based disease among populations that are endemic to parasitic worms (helminths) demonstrating the ability of these parasites to potentially regulate human immune responses. The aim of this systematic review and meta-analysis was to determine the impact of helminth infection on metabolic outcomes in human populations. Methods Using PRISMA guidelines, six databases were searched for studies published up to August 2020. Random effects meta-analysis was performed to estimate pooled proportions with 95% confidence intervals using the Review Manager Software version 5.4.1. Results Fourteen studies were included in the review. Fasting blood glucose was significantly lower in persons with infection (MD -0.22, 95% CI -0.40- -0.04, P=0.02), HbA1c levels were lower, although not significantly, and prevalence of the metabolic syndrome (P=0.001) and type 2 diabetes was lower (OR 1.03, 95% CI 0.34-3.09, P...
Background: Overexpression of sFlt-1 or modulation of FKBPL, key antiangiogenic proteins, are important in the pathogenesis of preeclampsia. Methods: A newly developed nonviral gene-delivery system, RALA, capable of overexpressing sFlt-1... more
Background: Overexpression of sFlt-1 or modulation of FKBPL, key antiangiogenic proteins, are important in the pathogenesis of preeclampsia. Methods: A newly developed nonviral gene-delivery system, RALA, capable of overexpressing sFlt-1 (e15a isoform) was delivered in vivo in transgenic haploinsufficient (Fkbpl+/-) mice. RALA was also used in vitro to deliver human Flt1 (hFlt1) in trophoblast cells. Results: Serum stable and nontoxic RALA/DNA-based nanoparticles induced an increase in sFlt-1 protein levels in the blood and total protein in the urine; the effect was more pronounced in Fkbpl+/- mice. In vitro, RALA-hFlt nanoparticles significantly reduced secretion of sFlt-1 in trophoblast cells. Conclusion: The RALA-based genetic nanodelivery system can be safely and effectively applied to emulate preeclampsia-like features or reduce sFlt-1 levels in vitro.
Preeclampsia is a multifactorial cardiovascular disorder diagnosed after 20 weeks of gestation, and is the leading cause of death for both mothers and babies in pregnancy. The pathophysiology remains poorly understood due to the... more
Preeclampsia is a multifactorial cardiovascular disorder diagnosed after 20 weeks of gestation, and is the leading cause of death for both mothers and babies in pregnancy. The pathophysiology remains poorly understood due to the variability and unpredictability of disease manifestation when studied in animal models. After preeclampsia, both mothers and offspring have a higher risk of cardiovascular disease (CVD), including myocardial infarction or heart attack and heart failure (HF). Myocardial infarction is an acute myocardial damage that can be treated through reperfusion; however, this therapeutic approach leads to ischemic/reperfusion injury (IRI), often leading to HF. In this review, we compared the current in vivo, in vitro and ex vivo model systems used to study preeclampsia, IRI and HF. Future studies aiming at evaluating CVD in preeclampsia patients could benefit from novel models that better mimic the complex scenario described in this article.
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Background Maternal smoking is currently a public health concern and has been associated with a number of complications in the offspring. E-cigarettes are gaining popularity as a ‘safer’ alternative to tobacco cigarettes during pregnancy,... more
Background Maternal smoking is currently a public health concern and has been associated with a number of complications in the offspring. E-cigarettes are gaining popularity as a ‘safer’ alternative to tobacco cigarettes during pregnancy, however, there are a limited number of studies to suggest that it is actually ‘safe’. Study Design Balb/C female mice were exposed to ambient air (n = 8; Sham), or tobacco cigarette smoke (n = 8; SE) before gestation, during gestation and lactation. A third group was exposed to cigarette smoke before gestation followed by e-cigarette aerosols during gestation and lactation (n = 8; Switch). Male offspring (12-week old, n = 10-14/group) underwent behavioural assessments to investigate short-term memory, anxiety and activity using the novel object recognition (NOR) and elevated plus maze (EPM) tests. Brains were collected at postnatal day (P)1, P20 and Week13 for global DNA methylation, epigenetic gene expression, and neuronal cell counts. Results The...
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The need to make higher education curricula gender-inclusive is increasingly pressing as student cohorts diversify. We adopted a student-staff partnership approach to design, integrate, and evaluate a module that taught first-year science... more
The need to make higher education curricula gender-inclusive is increasingly pressing as student cohorts diversify. We adopted a student-staff partnership approach to design, integrate, and evaluate a module that taught first-year science students the difference between biological sex, gender identity, gender expression, and sexual orientation in the context of genetics concepts at an Australian university. This module aimed to break the binary in misconceptions of both sex and gender, emphasising that both exist on separate spectra. Data triangulation was used to evaluate students’ attitudes towards the module and their learning of module concepts. Students’ attitudes were positive overall, and evaluation of students’ learning indicated that the majority of students understood and retained key concepts, while also identifying common misconceptions. Perhaps the most important finding was that students who identified as belonging to a minority group had significantly more positive at...
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Aims Circulating biomarkers are commonly used in diagnosis and prognosis of heart failure with preserved ejection fraction (HFpEF) in clinical practice. However, the diagnostic and prognostic potential of current biomarkers in HFpEF... more
Aims Circulating biomarkers are commonly used in diagnosis and prognosis of heart failure with preserved ejection fraction (HFpEF) in clinical practice. However, the diagnostic and prognostic potential of current biomarkers in HFpEF remain unclear. Methods and results We conducted a search of the PubMed, Web of Science, MEDLINE and SCOPUS (1900 to January 2020) databases of all diagnostic (n=1,104) and prognostic (n=53,497) biomarkers investigated in people with HFpEF. B-type natriuretic peptide (BNP) displayed satisfactory sensitivity (0.81, 95% CI: 0.76 to 0.85; I2=0) and specificity (0.86, 95% CI: 0.82 to 0.89; I2=16.9%) for the diagnosis of HFpEF. Natriuretic peptides (NPs), including N-terminal pro BNP (NT-proBNP) and BNP, were associated with over two-fold increased risk of mortality (NT-proBNP: HR=2.27, 95% CI: 1.69 to 3.06, I2=87.6%; BNP: HR=3.01, 95% CI: 1.27 to 7.21, I2=97.2%), hospitalisation (NT-proBNP: HR=3.54, 95% CI: 2.83 to 4.43, I2=83.4%), and a composite event of b...
Learning how to give and receive peer review is a skill that science students need support in developing. We included student peer review in an assessment for a large first year science subject. Class time was dedicated to introducing and... more
Learning how to give and receive peer review is a skill that science students need support in developing. We included student peer review in an assessment for a large first year science subject. Class time was dedicated to introducing and developing peer review skills and increasing engagement among students and between students and teachers. Students worked in pairs, small groups, and facilitated group discussions and were encouraged to learn from each other. The student peer review exercise provided students with the opportunity to reflect on and improve their work prior to submission. Survey results showed 78% of students agreed that peer review developed their ability to give constructive feedback. Training and resources provision for the teaching staff was crucial to the integration of peer review activities. Supported teaching staff were able to engage with and support the students, and the students valued this engagement and guidance.
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Obesity is a high risk for multiple metabolic disorders due to excessive influx of energy, glucose and lipid, often from a western based diet. Low-grade inflammation plays a key role in the progression of such metabolic disorders. The... more
Obesity is a high risk for multiple metabolic disorders due to excessive influx of energy, glucose and lipid, often from a western based diet. Low-grade inflammation plays a key role in the progression of such metabolic disorders. The anti-inflammatory property of gold compounds has been used in treating rheumatoid arthritis in the clinic. Previously we found that pure gold nanoparticles (AuNPs, 21 nm) also possess anti-inflammatory effects on the retroperitoneal fat tissue following intraperitoneal injection, by downregulating tumor necrosis factor (TNF) α. However, whether such an effect can change the risk of metabolic disorders in the obese has not been well studied. The study employed C57BL/6 mice fed a pellet high fat diet (HFD, 43% as fat) that were treated daily with AuNPs [low (HFD-LAu) or high (HFD-HAu) dose] via intraperitoneal injection for 9 weeks. In the in vitro study, RAW264.7 macrophages and 3T3-L1 adipocytes were cultured with low and high concentrations of AuNPs a...
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Both athletes and the general population use nutritional supplements. Athletes often turn to supplements hoping that consuming the supplement will help them be more competitive and healthy while the general population hopes to improve... more
Both athletes and the general population use nutritional supplements. Athletes often turn to supplements hoping that consuming the supplement will help them be more competitive and healthy while the general population hopes to improve body image or vitality. While many supplements contain ingredients that may have useful properties, there are supplements that are contaminated with compounds that are banned for use in sport or have been deliberately adulterated to fortify a supplement with an ingredient that will produce the advertised effect. In the present study, we have used yeast- and mammalian cell androgen bioassays to characterize the androgenic bioactivity of 112 sports supplements available from the Australian market, either over the counter or via the Internet. All 112 products did not declare an androgen on the label as an included ingredient. Our findings show that 6/112 supplements had strong androgenic bioactivity in the yeast cell bioassay, indicating products spiked o...
E-cigarette usage is increasing, especially among the young, with both the general population and physicians perceiving them as a safe alternative to tobacco smoking. Worryingly, e-cigarettes are commonly used by pregnant women. As... more
E-cigarette usage is increasing, especially among the young, with both the general population and physicians perceiving them as a safe alternative to tobacco smoking. Worryingly, e-cigarettes are commonly used by pregnant women. As nicotine is known to adversely affect children in-utero, we hypothesised that nicotine delivered via e-cigarettes would negatively affect lung development. To test this we developed a mouse model of maternal e-vapour (nicotine and nicotine-free) exposure, and investigated the impact on the growth and lung inflammation in both offspring and mothers. Female Balb/c mice were exposed to e-fluid vapour containing nicotine (E-cig18mg/mL, equivalent to 2 cigarettes/treatment, twice daily,) or nicotine free (E-cig0mg/mL) from 6 weeks prior to mating until pups weaned. Male offspring were studied at postnatal day (P) 1, 20 and at 13 weeks. The mothers were studied when the pups weaned. In the mothers' lung, e-cigarette exposure with and without nicotine increa...
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Vascular calcification is associated with increased risk of myocardial infarction and stroke. The objective of this work was to examine the ability of 17β-estradiol (E2) to stimulate calcification of vascular smooth muscle cells (VSMC) in... more
Vascular calcification is associated with increased risk of myocardial infarction and stroke. The objective of this work was to examine the ability of 17β-estradiol (E2) to stimulate calcification of vascular smooth muscle cells (VSMC) in vivo, using aged apolipoprotein E-null mice with advanced atherosclerotic lesions, and subsequently to explore underlying mechanisms in vitro. Silastic E2 capsules were implanted into male and female apolipoprotein E-null mice aged 34 weeks. Plaque and calcified area were measured in the aortic sinus and innominate artery after 8 weeks. Immunohistochemical analysis examined expression of the estrogen receptors (estrogen receptor alpha and estrogen receptor beta [ERβ]). VSMC expression of osteogenic markers was examined using digital polymerase chain reaction. Advanced atherosclerotic lesions were present in all mice at the end of 8 weeks. In both male and female mice, E2 increased calcified area in a site-specific manner in the aortic sinus indepen...
Research Interests: Atherosclerosis, Cell Differentiation, Humans, Collagen, Female, and 15 moreAnimals, Male, Osteocalcin, Osteopontin, Phenotype, Clinical Sciences, Cattle, Osteogenesis, Calcium Binding Proteins, Estradiol, Neointima, Extracellular Matrix Proteins, Estrogen receptor alpha, Estrogen Receptor beta, and Cardiovascular medicine and haematology
Sport supplements containing steroids never approved for therapeutic use have the potential for abuse by athletes. Most are marketed online and may contain undisclosed steroids yet are readily available despite lacking toxicological or... more
Sport supplements containing steroids never approved for therapeutic use have the potential for abuse by athletes. Most are marketed online and may contain undisclosed steroids yet are readily available despite lacking toxicological or pharmacological evaluation. In this study, 18 supplements purchased online underwent organic solvent extraction to isolate any steroids they contained. From the 18 supplements, 19 steroids were identified and for each, its intrinsic androgenic potency was determined by a yeast cell (Saccharomyces cerevisiae) androgen bioassay and its potential androgenic potency was determined by a liver (HuH7) cell androgen bioassay. The yeast bioassay showed that of the 19 steroids tested, 6 demonstrated strong intrinsic bioactivity, with 4 metabolically activated to even stronger androgens. Moreover, 4 steroids with moderate and 1 with intrinsically weak androgenic bioactivity were activated to more potent androgens. Finally, 8 steroids were metabolically inactivated or deactivated into weaker androgens. Our results show that Internet-sourced sport supplements may contain intrinsically strong androgens, or precursors that can be metabolized to them. These potentially potent pharmacologically active steroids are being used without regulatory control or consumer awareness of their potential adverse effects. Copyright © 2016 John Wiley &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp; Sons, Ltd.
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Research Interests: Endocrinology, Cell Adhesion, Biological Sciences, Humans, Female, and 15 moreMale, Gender Difference, Androgens, mRNA stability, Aged, Middle Aged, Peripheral Vascular Disease, Adult, Time Dependent, Endothelial cell, Monocytes, Androgen Receptor, Dihydrotestosterone, Sex Characteristics, and Medical and Health Sciences
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Anecdotal evidence suggests that male sex hormones are proatherogenic. We hypothesized that the male sex hormone receptor, the androgen receptor (AR), acts as a molecular switch in sex-specific inflammatory signaling in vascular cells. AR... more
Anecdotal evidence suggests that male sex hormones are proatherogenic. We hypothesized that the male sex hormone receptor, the androgen receptor (AR), acts as a molecular switch in sex-specific inflammatory signaling in vascular cells. AR expression in human umbilical vein endothelial cells (HUVECs), human monocyte-derived macrophages (MDMs) or HeLa cells was modulated by transfection with AR siRNA or human AR cDNA expression vector. Activity and expression levels were measured by luciferase reporter assays, Western blotting or real-time PCR analysis. AR knockdown reduced expression of vascular cell adhesion molecule-1 (VCAM-1) in genetically male HUVECs. Conversely, AR upregulation in genetically female HUVECs induced VCAM-1 expression and increased dihydrotestosterone-stimulated monocyte adhesion. Co-transfection of an AR expression vector with VCAM-1 or NF-κB-reporter vectors into phenotypically female, AR-negative HeLa cells confirmed AR regulation of VCAM-1 expression as well as AR activation of NF-κB. AR upregulation was not sufficient to increase ICAM-1 levels in female HUVECs or lipoprotein metabolism gene expression in female MDMs, despite AR knockdown limiting expression in their male counterparts. AR acts as a molecular switch to induce VCAM-1 expression. Low AR levels in female HUVECs limit NF-κB/VCAM-1 induction and monocyte adhesion and could contribute to the gender bias in cardiovascular disease. Unidentified factors in female cells limit induction of other proatherogenic genes not primarily regulated by NF-κB.
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Oxidative stress and inflammation, leading to endothelial dysfunction, contribute to the pathogenesis of atherosclerosis. The popularity of natural product supplements has increased in recent years, especially those with purported... more
Oxidative stress and inflammation, leading to endothelial dysfunction, contribute to the pathogenesis of atherosclerosis. The popularity of natural product supplements has increased in recent years, especially those with purported anti-inflammatory and/or antioxidant effects. The efficacy and mechanism of many of these products are not yet well understood. In this study, we tested the antioxidant and anti-inflammatory effects of a supplement, HIPER Health Supplement (HIPER), on cytokine-induced inflammation and oxidative stress in human coronary artery endothelial cells (HCAECs). HIPER is a mixture of French maritime pine bark extract (PBE), honey, aloe vera, and papaya extract. Treatment for 24 hours with HIPER reduced TNF-α-induced reactive oxygen species (ROS) generation that was associated with decreased NADPH oxidase 4 and increased superoxide dismutase-1 expression. HIPER inhibited TNF-α induced monocyte adhesion to HCAECs that was in keeping with decreased expression of vascular cell adhesion molecule-1 and intercellular cell adhesion molecule-1 and decreased nuclear factor-kappa B (NF-κB) activation. Further investigation of mechanism showed HIPER reduced TNF-α induced IκBα and p38 and MEK1/2 MAP kinases phosphorylation. Our findings show that HIPER has potent inhibitory effects on HCAECs inflammatory and oxidative stress responses that may protect against endothelial dysfunction that underlies early atherosclerotic lesion formation.
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Anecdotal evidence suggests that male sex hormones are proatherogenic. We hypothesized that the male sex hormone receptor, the androgen receptor (AR), acts as a molecular switch in sex-specific inflammatory signaling in vascular cells. AR... more
Anecdotal evidence suggests that male sex hormones are proatherogenic. We hypothesized that the male sex hormone receptor, the androgen receptor (AR), acts as a molecular switch in sex-specific inflammatory signaling in vascular cells. AR expression in human umbilical vein endothelial cells (HUVECs), human monocyte-derived macrophages (MDMs) or HeLa cells was modulated by transfection with AR siRNA or human AR cDNA expression vector. Activity and expression levels were measured by luciferase reporter assays, Western blotting or real-time PCR analysis. AR knockdown reduced expression of vascular cell adhesion molecule-1 (VCAM-1) in genetically male HUVECs. Conversely, AR upregulation in genetically female HUVECs induced VCAM-1 expression and increased dihydrotestosterone-stimulated monocyte adhesion. Co-transfection of an AR expression vector with VCAM-1 or NF-κB-reporter vectors into phenotypically female, AR-negative HeLa cells confirmed AR regulation of VCAM-1 expression as well a...