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View article: High-throughput drug screening identifies EGFR/MAPK pathway targeting sensitivities in organoid models of ovarian carcinosarcoma
High-throughput drug screening identifies EGFR/MAPK pathway targeting sensitivities in organoid models of ovarian carcinosarcoma Open
Background Ovarian carcinosarcoma (OCS) is a rare and aggressive tumour type with limited treatment options. Standard therapy includes platinum agents, but responses are poor. OCS highly express mesenchymal markers, such as N-MYC and HMGA2…
View article: Amniotic Fluid Extracellular Vesicle Properties Evolve With Gestational Age and Reflect Fetal Development
Amniotic Fluid Extracellular Vesicle Properties Evolve With Gestational Age and Reflect Fetal Development Open
Amniotic fluid (AF) is a valuable source of extracellular vesicles (EVs) derived from the fetoplacental unit. Preclinical and clinical studies have highlighted promising applications of AF‐EVs and their role in cellular communication, yet …
View article: Postpartum administration of eplerenone to mitigate vascular dysfunction in mice following a preeclampsia-like pregnancy
Postpartum administration of eplerenone to mitigate vascular dysfunction in mice following a preeclampsia-like pregnancy Open
Preeclampsia is a severe pregnancy complication associated with substantial injury to systemic vasculature, major organs, and the feto-placental unit, with an approximate mortality rate of 76,000 pregnant women and 500,000 babies each year…
View article: First-trimester exposure to anti-cytomegalovirus medications: a study of the effects of valaciclovir, letermovir and maribavir on early placental development
First-trimester exposure to anti-cytomegalovirus medications: a study of the effects of valaciclovir, letermovir and maribavir on early placental development Open
Congenital cytomegalovirus (CMV) infection is the leading preventable cause of childhood disability, including sensorineural hearing loss and cerebral palsy in high-income countries. Early maternal treatment with valaciclovir has been show…
View article: Investigating the Impact of Maternal Obesity on Disease Severity in a Mouse Model of Preeclampsia
Investigating the Impact of Maternal Obesity on Disease Severity in a Mouse Model of Preeclampsia Open
Background: Preeclampsia is a leading cause of maternal and fetal morbidity and mortality, with obesity recognised as a significant risk factor. However, the direct contribution of obesity to the pathophysiology underpinning preeclampsia r…
View article: Amniotic fluid extracellular vesicle properties evolve with gestational age and reflect fetal development
Amniotic fluid extracellular vesicle properties evolve with gestational age and reflect fetal development Open
Amniotic fluid (AF) is a valuable source of extracellular vesicles (EVs) derived from the fetoplacental unit. Preclinical and clinical studies have highlighted promising applications of AF-EVs and their role in cellular communication, yet …
View article: Demethylating agents drive PARP inhibitor resistance in ovarian carcinomas with BRCA1 gene silencing
Demethylating agents drive PARP inhibitor resistance in ovarian carcinomas with BRCA1 gene silencing Open
DNA methyltransferase 1 inhibitor (DNMT1i) therapy is a promising option for increasing immune response as part of combination cancer therapy. High–grade serous ovarian carcinoma (HGSOC) is a highly aggressive cancer with poor survival out…
View article: Phosphoglucomutase 5 gene transcripts are expressed by the human placenta and differentially regulated in placental dysfunction
Phosphoglucomutase 5 gene transcripts are expressed by the human placenta and differentially regulated in placental dysfunction Open
The placenta plays an essential role facilitating nutrient, gas and waste exchange between the maternal and fetal systems for optimal fetal growth. When placental development is impaired and the placenta dysfunctional, serious pregnancy co…
View article: Generation of a PARPi-sensitive homozygous BRCA1-methylated OVCAR8 cell line using targeted CRISPR gene editing
Generation of a PARPi-sensitive homozygous BRCA1-methylated OVCAR8 cell line using targeted CRISPR gene editing Open
Up to 17% of high grade serous ovarian carcinomas (HGSOC) harbour BRCA1 promoter methylation (meBRCA1), making them susceptible to treatment with targeted PARP inhibitor (PARPi) therapy. Unfortunately, meBRCA1 loss can be acquired followin…
View article: The effect of anti-thrombotic therapy on cell-free DNA release from first- and third-trimester placental explants: insights into the mechanism of non-invasive prenatal test (NIPT) failures
The effect of anti-thrombotic therapy on cell-free DNA release from first- and third-trimester placental explants: insights into the mechanism of non-invasive prenatal test (NIPT) failures Open
Objective: Low molecular weight heparins, including enoxaparin, have been associated with increased non-invasive prenatal testing (NIPT) failures due to low fetal fraction of cell-free (cf) DNA. This study investigated the effect of enoxap…
View article: The Regulation of Endothelin-1 in Pregnancies Complicated by Gestational Diabetes: Uncovering the Vascular Effects of Insulin
The Regulation of Endothelin-1 in Pregnancies Complicated by Gestational Diabetes: Uncovering the Vascular Effects of Insulin Open
Gestational diabetes mellitus (GDM) is a condition of pregnancy defined by new-onset hyperglycemia. GDM is associated with impaired maternal endothelial and vascular reactivity. Endothelin-1 (ET-1) is a potent vasoconstrictor that contribu…
View article: Investigating the Effects of Atrial Natriuretic Peptide on the Maternal Endothelium to Determine Potential Implications for Preeclampsia
Investigating the Effects of Atrial Natriuretic Peptide on the Maternal Endothelium to Determine Potential Implications for Preeclampsia Open
Preeclampsia is associated with an increased lifelong risk of cardiovascular disease (CVD). It is not clear whether this is induced by persistent systemic organ and vascular damage following preeclampsia or due to a predisposition to both …
View article: Hydroxychloroquine reduces soluble Flt-1 secretion from human cytotrophoblast, but does not mitigate markers of endothelial dysfunction in vitro
Hydroxychloroquine reduces soluble Flt-1 secretion from human cytotrophoblast, but does not mitigate markers of endothelial dysfunction in vitro Open
Preeclampsia is a multi-system disease that can have severe, even fatal implications for the mother and fetus. Abnormal placentation can lead to ischaemic tissue injury and placental inflammation. In turn, the placenta releases anti-angiog…
View article: Serum Collected from Preeclamptic Pregnancies Drives Vasoconstriction of Human Omental Arteries—A Novel Ex Vivo Model of Preeclampsia for Therapeutic Development
Serum Collected from Preeclamptic Pregnancies Drives Vasoconstriction of Human Omental Arteries—A Novel Ex Vivo Model of Preeclampsia for Therapeutic Development Open
New-onset maternal hypertension is a hallmark of preeclampsia, driven by widespread endothelial dysfunction and systemic vasoconstriction. Here, we set out to create a new ex vivo model using preeclamptic serum to cause injury to the endot…
View article: Placental OLAH Levels Are Altered in Fetal Growth Restriction, Preeclampsia and Models of Placental Dysfunction
Placental OLAH Levels Are Altered in Fetal Growth Restriction, Preeclampsia and Models of Placental Dysfunction Open
Previously, we identified elevated transcripts for the gene Oleoyl-ACP Hydrolase (OLAH) in the maternal circulation of pregnancies complicated by preterm fetal growth restriction. As placental dysfunction is central to the pathogenesis of …
View article: Assessment of the Proton Pump Inhibitor, Esomeprazole Magnesium Hydrate and Trihydrate, on Pathophysiological Markers of Preeclampsia in Preclinical Human Models of Disease
Assessment of the Proton Pump Inhibitor, Esomeprazole Magnesium Hydrate and Trihydrate, on Pathophysiological Markers of Preeclampsia in Preclinical Human Models of Disease Open
Previously, we demonstrated that the proton pump inhibitor, esomeprazole magnesium hydrate (MH), could have potential as a repurposed treatment against preeclampsia, a serious obstetric condition. In this study we investigate the differenc…
View article: The L-NAME mouse model of preeclampsia and impact to long-term maternal cardiovascular health
The L-NAME mouse model of preeclampsia and impact to long-term maternal cardiovascular health Open
Preeclampsia affects ∼2–8% of pregnancies worldwide. It is associated with increased long-term maternal cardiovascular disease risk. This study assesses the effect of the vasoconstrictor N(ω)-nitro-L-arginine methyl ester (L-NAME) in model…
View article: Actions of Esomeprazole on the Maternal Vasculature in Lean and Obese Pregnant Mice with Impaired Nitric Oxide Synthesis: A Model of Preeclampsia
Actions of Esomeprazole on the Maternal Vasculature in Lean and Obese Pregnant Mice with Impaired Nitric Oxide Synthesis: A Model of Preeclampsia Open
Preeclampsia is a devastating, multisystem disorder of pregnancy. It has no cure except delivery, which if premature can impart significant neonatal morbidity. Efforts to repurpose pregnancy-safe therapeutics for the treatment of preeclamp…
View article: RNAseq of amniotic fluid cell-free RNA: insights into the pathophysiology of congenital cytomegalovirus infection
RNAseq of amniotic fluid cell-free RNA: insights into the pathophysiology of congenital cytomegalovirus infection Open
Background Congenital cytomegalovirus (cCMV) is the most common perinatal infection and a significant cause of sensorineural hearing loss, cerebral palsy and neurodevelopmental disability. There is a paucity of human gene expression studie…
View article: Pre-Clinical Investigation of Cardioprotective Beta-Blockers as a Therapeutic Strategy for Preeclampsia
Pre-Clinical Investigation of Cardioprotective Beta-Blockers as a Therapeutic Strategy for Preeclampsia Open
Despite significant maternal and fetal morbidity, a treatment for preeclampsia currently remains an unmet need in clinical care. As too does the lifelong cardiovascular risks imparted on preeclampsia sufferers. Endothelial dysfunction and …
View article: Melatonin enhances antioxidant molecules in the placenta, reduces secretion of soluble fms-like tyrosine kinase 1 (sFLT) from primary trophoblast but does not rescue endothelial dysfunction: An evaluation of its potential to treat preeclampsia
Melatonin enhances antioxidant molecules in the placenta, reduces secretion of soluble fms-like tyrosine kinase 1 (sFLT) from primary trophoblast but does not rescue endothelial dysfunction: An evaluation of its potential to treat preeclampsia Open
Preeclampsia is one of the most serious complications of pregnancy. Currently there are no medical treatments. Given placental oxidative stress may be an early trigger in the pathogenesis of preeclampsia, therapies that enhance antioxidant…