Publications
105 results found
Mountain K, MacIntyre D, Chan D, et al., 2023, ABO blood group antigens and preterm birth risk, 12th International Workshop Reunion Island Reproductive Immunology, Immunological tolerance and Immunology of preeclampsia, Publisher: ELSEVIER IRELAND LTD, Pages: 37-37, ISSN: 0165-0378
Gimeno-Molina B, Bayar E, Mountain K, et al., 2023, The role of cervical neutrophils in cervicovaginal inflammation in women at high-risk of delivering preterm, 12th International Workshop Reunion Island Reproductive Immunology, Immunological tolerance and Immunology of preeclampsia, Publisher: ELSEVIER IRELAND LTD, Pages: 31-31, ISSN: 0165-0378
Riaposova L, Kim SH, Hanyaloglu A, et al., 2023, Prostaglandin F2alpha requires activation of calcium-dependent signalling to trigger inflammation in human myometrium, Frontiers in Endocrinology, Vol: 14, Pages: 1-19, ISSN: 1664-2392
Introduction: Preterm birth is one of the major causes of neonatal morbidity and mortality across the world. Both term and preterm labour are preceded by inflammatory activation in uterine tissues. This includes increased leukocyte infiltration, and subsequent increase in chemokine and cytokine levels, activation of pro-inflammatory transcription factors as NF-κB and increased prostaglandin synthesis. Prostaglandin F2α (PGF2α) is one of the myometrial activators and stimulators.Methods: Here we investigated the role of PGF2α in pro-inflammatory signalling pathways in human myometrial cells isolated from term non-labouring uterine tissue. Primary myometrial cells were treated with G protein inhibitors, calcium chelators and/or PGF2α. Nuclear extracts were analysed by TranSignal cAMP/Calcium Protein/DNA Array. Whole cell protein lysates were analysed by Western blotting. mRNA levels of target genes were analysed by RT-PCR.Results: The results show that PGF2α increases inflammation in myometrial cells through increased activation of NF-κB and MAP kinases and increased expression of COX-2. PGF2α was found to activate several calcium/cAMP-dependent transcription factors, such as CREB and C/EBP-β. mRNA levels of NF-κB-regulated cytokines and chemokines were also elevated with PGF2α stimulation. We have shown that the increase in PGF2α-mediated COX-2 expression in myometrial cells requires coupling of the FP receptor to both Gαq and Gαi proteins. Additionally, PGF2α-induced calcium response was also mediated through Gαq and Gαi coupling.Discussion: In summary, our findings suggest that PGF2α-induced inflammation in myometrial cells involves activation of several transcription factors – NF-κB, MAP kinases, CREB and C/EBP-β. Our results indicate that the FP receptor signals via Gαq and Gαi coupling in myometrium. This work provides insight i
Halim S, Mulla K, Avari P, et al., 2023, Retrospective review of intra-partum care and neonatal outcomes of mothers with pre-gestational diabetes at St Mary's Hospital, London, Publisher: WILEY, ISSN: 0742-3071
Bayar E, MacIntyre D, Sykes L, et al., 2023, Safety, tolerability and acceptability of Lactobacillus crispatus CTV-05 (LACTIN-V) in pregnant women at high-risk of preterm birth, Beneficial Microbes, ISSN: 1876-2883
The vaginal microbiota is a determinant for the risk of preterm birth (PTB). Dominance of the vaginal niche by Lactobacillus crispatus associates with term delivery. This is the first observational clinical study of live vaginal biotherapeutics (Lactobacillus crispatus CTV-05 (LACTIN-V), Osel, California, USA) in pregnant women at high-risk of PTB. The primary aim was to explore safety, tolerability and acceptability of LACTIN-V in pregnancy. Women were offered a course of LACTIN-V at 14 weeks gestation for five consecutive days followed by weekly administration for six weeks. Participants were followed up at 15, 18-, 20-, 28- and 36-weeks’ gestation and at delivery for assessment of adverse events, compliance and tolerability. Participants completed a questionnaire to gauge experience and acceptability. In total, 73 women were recruited, of whom eight withdrew, leaving a final cohort size of 61. Self-reported compliance to the course was high (56/60, 93%). Solicited adverse events were reported in 13 women (19%) including changes in vaginal discharge, odour, colour or consistency of urine, itching and vaginal bleeding. One unsolicited adverse event was reported as haematuria at 38 weeks gestation, but was judged to be unrelated to LACTIN-V. No serious adverse events occurred. One mild adverse event led to study withdrawal. Thirty-one women completed an experience and acceptability questionnaire. Women found LACTIN-V easy and comfortable to use and the majority (30/31, 97%) would use LACTIN-V in future pregnancies. Eight women (8/31, 26%) found the schedule of use difficult to remember. The rate of PTB <34 weeks in this cohort was 3.3% compared to 7% in a historical cohort of 2,190 women at similar background PTB risk. With satisfactory uptake and good compliance, we demonstrate that LACTIN-V is safe and accepted in pregnancy, with high tolerability. Further studies are needed to assess colonisation of Lactobacillus crispatus CTV-05 and clinical efficacy.
Ng S, Mountain KE, Elger T, et al., 2023, Predictive Value of Cervical Length Screening in the Context of Cervical Cerclage: A Cohort Study, 70th Annual Meeting of the Society for Reproductive Investigation (SRI), Publisher: SPRINGER HEIDELBERG, Pages: 109A-110A, ISSN: 1933-7191
Molina BG, Bayar E, Love RL, et al., 2023, Cervical Shortening is Associated with Cervical Neutrophil Migration and Complement Activation, 70th Annual Meeting of the Society for Reproductive Investigation (SRI), Publisher: SPRINGER HEIDELBERG, Pages: 94A-95A, ISSN: 1933-7191
Petrou L, Gatehouse A, Kim SH, et al., 2023, Detection of miR-374a-5p on Magnetic Microbeads as a Predictor of Small for Gestational Age Births, 70th Annual Meeting of the Society for Reproductive Investigation (SRI), Publisher: SPRINGER HEIDELBERG, Pages: 208A-209A, ISSN: 1933-7191
Beleil TO, Brown RG, Hudacova E, et al., 2023, Spatial Characterisation of the Reproductive Tract Microbiota Indicates High Prevalence of Microbial Driven Aetiology in PPROM, 70th Annual Meeting of the Society for Reproductive Investigation (SRI), Publisher: SPRINGER HEIDELBERG, Pages: 48A-48A, ISSN: 1933-7191
Kim SH, Arianoglou M, MacIntyre DA, et al., 2023, Validation of Circulating MicroRNA Markers for Prediction of Small-for-Gestational-Age Births, 70th Annual Meeting of the Society for Reproductive Investigation (SRI), Publisher: SPRINGER HEIDELBERG, Pages: 166A-167A, ISSN: 1933-7191
Gimeno Molina B, Bennett P, MacIntyre D, et al., 2022, Preterm birth and the vaginal microbiomes, Recent Advances in Obstetrics & Gynaecology - 28, Editors: Das, Tulandi, Publisher: JP Medical, ISBN: 9781787791732
Wu G, Grassi P, MacIntyre D, et al., 2022, N-Glycosylation of cervicovaginal fluid reflects microbial community, immune activity, and pregnancy status, Scientific Reports, Vol: 12, Pages: 1-14, ISSN: 2045-2322
Human cervicovaginal fluid (CVF) is a complex, functionally important and glycan rich biological fluid, fundamental in mediating physiological events associated with reproductive health. Using a comprehensive glycomic strategy we reveal an extremely rich and complex N-glycome in CVF of pregnant and non-pregnant women, abundant in paucimannose and highmannose glycans, complex glycans with 2-4 N-Acetyllactosamine (LacNAc) antennae, and Poly-LacNAc glycans decorated with fucosylation and sialylation. N-glycosylation variations were observed to differ in relation to pregnancy status, microbial composition, immune activation, and pregnancy outcome. Compared to CVF from women experiencing term birth, CVF from women who subsequently experienced preterm birth showed lower sialylation, which correlated to the presence of a diverse microbiome, and higher fucosylation, which correlated positively to pro-inflammatory cytokine concentration. This study is the first step towards better understanding the role of cervicovaginal glycans in reproductive health, their contribution to the mechanism of microbial driven preterm birth, and their potential forpreventative therapy.
Ho AEP, Rasheed ZBM, Norman J, et al., 2022, Rhombencephalitis in Pregnancy-A Challenging Case of Probable <i>Listeria</i> Infection, LIFE-BASEL, Vol: 12
Gimeno-Molina B, Muller I, Kropf P, et al., 2022, The role of neutrophils in pregnancy, term and preterm labour, Life, Vol: 12, ISSN: 2075-1729
Neutrophils are surveillance cells, and the first to react and migrate to sites of inflammation and infection following a chemotactic gradient. Neutrophils play a key role in both sterile inflammation and infection, performing a wide variety of effector functions such as degranulation, phagocytosis, ROS production and release of neutrophil extracellular traps (NETs). Healthy term labour requires a sterile pro-inflammatory process, whereas one of the most common causes of spontaneous preterm birth is microbial driven. Peripheral neutrophilia has long been described during pregnancy, and evidence exists demonstrating neutrophils infiltrating the cervix, uterus and foetal membranes during both term and preterm deliveries. Their presence supports a role in tissue remodelling via their effector functions. In this review, we describe the effector functions of neutrophils. We summarise the evidence to support their role in healthy pregnancy and labour and describe their potential contribution to microbial driven preterm birth.
Rasheed Z, Lee Y, Kim S, et al., 2022, 15-Deoxy-Delta-12,14-prostaglandin J2 modulates pro-labour and pro-inflammatory responses in human myocytes, vaginal and amnion epithelial cells, Frontiers in Endocrinology, Vol: 13, ISSN: 1664-2392
Background: Prematurity is the leading cause of childhood death under the age of five. The aetiology of preterm birth is multifactorial; however, inflammation and infection are the most common causal factors, supporting a potential role for immunomodulation as a therapeutic strategy. 15-Deoxy-Delta-12,14-prostaglandin J2 (15dPGJ2) is an anti-inflammatory prostaglandin and has been shown to delay lipopolysaccharide (LPS) induced preterm labour in mice and improve pup survival. This study exploresthe immunomodulatory effect of 15dPGJ2 on the transcription factors NF-κB and AP-1, pro-inflammatory cytokines, and contraction associated proteins in human cultured myocytes, vaginal epithelial cell line (VECs) and primary amnion epithelial cells (AECs).Methods: Cells were pre-incubated with 32μM of 15dPGJ2 and stimulated with 1ng/mL of IL-1β as an in vitro model of inflammation. Western immunoblotting was used to detect phosphorylated p-65 and phosphorylated c-Jun as markers of NF-κB and AP-1 activation, respectively. mRNA expression of the pro-inflammatory cytokines IL-6, IL-8, and TNF-α was examined, and protein expression of COX-2 and PGE2 were detected by western immunoblotting and ELISA respectively. Myometrial contractility wasexamined ex-vivo using a myograph.Results:15dPGJ2 inhibited IL-1β-induced activation of NF-κB and AP-1, and expression of IL-6, IL-8, TNF-α, COX-2 and PGE2 in myocytes, with no effect on myometrial contractility or cell viability. Despite inhibiting IL-1β-induced activation of NF-κB, expression of IL-6, TNF-α, and COX-2, 15dPGJ2 led to activation of AP-1, increased production of PGE2 and increased cell death in VECs and AECs.Conclusion: We conclude that 15dPGJ2 has differential effects on inflammatory modulation depending on cell type and is therefore unlikely to be a useful therapeutic agent for the prevention of preterm birth.
Petrou L, Latvanen E, Seichepine F, et al., 2022, Lateral Flow Test (LFT) detects cell-free microRNAs predictive of preterm birth directly from human plasma, Advanced NanoBiomed Research, Vol: 2, ISSN: 2699-9307
Despite extensive research toward the development of point-of-care nucleic acid tests (POC NATs) for the detection of microRNAs (miRs) from liquid biopsies, major hurdles remain including the strict requirement for extensive off-chip sample preprocessing. Herein, a nucleic acid lateral flow test (NALFT) is reported on that enables the direct detection of endogenous miRs from as little as 3 μL of plasma without the requirement for any enzyme-catalyzed target amplification or complex miR extraction steps. This is achieved through integration of a denaturing hydrogel composite material onto the LFT, allowing for near-instantaneous on-chip release of miRs from their carriers (extracellular vesicles or transport proteins) prior to detection. This next-generation LFT is sensitive enough to detect endogenous concentrations of miR-150-5p, a predictive biomarker for preterm birth (PTB) found deregulated in maternal blood from as early as 12th week of pregnancy. Herein, a key step is represented toward a first bedside test for risk-stratification during pregnancy by predicting true outcome at a very early stage. More generally, the universal and versatile nature of this novel sample preprocessing platform can further improve the robustness of existing NALFTs and facilitate their application at the POC.
Molina B, Bayar E, Lee Y, et al., 2022, Cervicovaginal inflammation and neutrophil infiltration/activation in women at high-risk of prematurity, Publisher: WILEY, Pages: 54-54, ISSN: 1470-0328
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Bayar E, MacIntyre D, Sykes L, et al., 2022, Safety, tolerability and acceptability of <i>Lactobacillus crispatus</i> CTV-05 (LACTIN-V) in pregnancy, Publisher: WILEY, Pages: 53-53, ISSN: 1470-0328
Bayar E, Brown R, Chan D, et al., 2022, Do emergency cervical cerclages save babies lives?, Publisher: WILEY, Pages: 48-49, ISSN: 1470-0328
Mountain K, MacIntyre D, Chan D, et al., 2022, Blood group antigens influence host-microbe interactions and risk of early preterm birth, Publisher: WILEY, Pages: 55-56, ISSN: 1470-0328
MacIntyre DA, Pruski P, Correia G, et al., 2022, Rapid Assessment of Vaginal Microbiota Host Interactions During Pregnancy and Preterm Birth by Direct On-Swab Desorption Electrospray Ionization Mass Spectrometry, Publisher: SPRINGER HEIDELBERG, Pages: 53-53, ISSN: 1933-7191
Wang YY, Hirani D, Agha-Jaffar R, et al., 2022, Gestational diabetes increase associated with covid-19 pandemic in an inner-city multi-ethnic cohort, Publisher: WILEY, ISSN: 0742-3071
Kundu S, Lee Y, Sykes L, et al., 2022, The Effect of Secretor Status and the Vaginal Microbiome on Birth Outcome, Publisher: SPRINGER HEIDELBERG, Pages: 197-197, ISSN: 1933-7191
Chan D, Bennett P, Lee YS, et al., 2022, Microbial-driven preterm labour involves crosstalk between the innate and adaptive immune response, Nature Communications, Vol: 13, ISSN: 2041-1723
There has been a surge in studies implicating a role of vaginal microbiota in spontaneous preterm birth (sPTB), but most are associative without mechanistic insight. Here we show a comprehensive approach to understand the causative factors of preterm birth, based on the integration of longitudinal vaginal microbiota and cervicovaginal fluid (CVF) immunophenotype data collected from 133 women at high-risk of sPTB. We show that vaginal depletion of Lactobacillus species and high bacterial diversity leads to increased mannose binding lectin (MBL), IgM, IgG, C3b, C5, IL-8, IL-6 and IL-1β and to increased risk of sPTB. Cervical shortening, which often precedes preterm birth, is associated with Lactobacillus iners and elevated levels of IgM, C3b, C5, C5a and IL-6. These data demonstrate a role for the complement system in microbial-driven sPTB and provide a scientific rationale for the development of live biotherapeutics and complement therapeutics to prevent sPTB.
Kim SH, MacIntyre D, Sykes L, et al., 2022, Whole blood holding time prior to plasma processing alters microRNA expression profile, Frontiers in Genetics, Vol: 12, ISSN: 1664-8021
MicroRNAs (miRNAs) can exhibit aberrant expression under different physiological and pathological conditions. Therefore, differentially expressed circulating miRNAs have been a focus of biomarker discovery research. However, the use of circulating miRNAs comes with challenges which may hinder the reliability for their clinical application. These include varied sample collection protocols, storage times/conditions, sample processing and analysis methods. This study focused on examining the effect of whole blood holding time on the stability of plasma miRNA expression profiles. Whole blood samples were collected from healthy pregnant women and were held at 4°C for 30 min, 2 h, 6 h or 24 h prior to processing for plasma isolation. Plasma RNA was extracted and the expression of 179 miRNAs were analyzed. Unsupervised principal component analysis demonstrated that whole blood holding time was a major source of variation in miRNA expression profiles with 53 of 179 miRNAs showing significant changes in expression. Levels of specific miRNAs previously reported to be associated with pregnancy-associated complications such as hsa-miR-150-5p, hsa-miR-191-5p, and hsa-miR-29a-3p, as well as commonly used endogenous miRNA controls, hsa-miR-16-5p, hsa-miR-25-3p, and hsa-miR-223-3p were significantly altered with increase in blood holding time. Current protocols for plasma-based miRNA profiling for diagnostics describe major differences in whole blood holding periods ranging from immediately after collection to 26 h after. Our results demonstrate holding time can have dramatic effects on analytical reliability and reproducibility. This highlights the importance of standardization of blood holding time prior to processing for plasma in order to minimize introduction of non-biological variance in miRNA profiles.
Pruski P, Dos Santos Correia G, Lewis H, et al., 2021, Direct on-swab metabolic profiling of vaginal microbiome host interactions during pregnancy and preterm birth, Nature Communications, Vol: 12, ISSN: 2041-1723
The pregnancy vaginal microbiome contributes to risk of preterm birth, the primary cause of death in children under 5 years of age. Here we describe direct on-swab metabolic profiling by Desorption Electrospray Ionization Mass Spectrometry (DESI-MS) for sample preparation-free characterisation of the cervicovaginal metabolome in two independent pregnancy cohorts (VMET, n = 160; 455 swabs; VMET II, n = 205; 573 swabs). By integrating metataxonomics and immune profiling data from matched samples, we show that specific metabolome signatures can be used to robustly predict simultaneously both the composition of the vaginal microbiome and host inflammatory status. In these patients, vaginal microbiota instability and innate immune activation, as predicted using DESI-MS, associated with preterm birth, including in women receiving cervical cerclage for preterm birth prevention. These findings highlight direct on-swab metabolic profiling by DESI-MS as an innovative approach for preterm birth risk stratification through rapid assessment of vaginal microbiota-host dynamics.
Hirani D, Ladha T, Tan M, et al., 2021, Diagnosing gestational diabetes: COVID-19 criteria vs oral glucose tolerance test, Publisher: SPRINGER, Pages: 177-178, ISSN: 0012-186X
Chan D, Bennett PR, Lee YS, et al., 2021, Microbial-Driven Preterm Labour Involves Crosstalk between the Innate and Adaptive Immune Response., Publisher: SPRINGER HEIDELBERG, Pages: 108A-109A, ISSN: 1933-7191
Bayar E, Zarasvand S, Adan M, et al., 2021, Acceptability of live vaginal biotherapeutics in a cohort of pregnant women, Publisher: WILEY, Pages: E32-E33, ISSN: 1470-0328
Budwig L, Brown R, Lee YS, et al., 2021, The Use of Peripheral Blood Neutrophil Counts in the Prediction of Funisitis Following Preterm Prelabour Rupture of Membranes., Publisher: SPRINGER HEIDELBERG, Pages: 116A-116A, ISSN: 1933-7191
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