1.
The bivariate NRIP1/ZEB2 RNA marker permits non-invasive presymptomatic screening of pre-eclampsia.
Manders, V, Visser, A, Keijser, R, Min, N, Poutsma, A, Mulders, J, van den Berkmortel, T, Hortensius, M, Jongejan, A, Pajkrt, E, et al
Scientific reports. 2020;(1):21857
Abstract
Using genome-wide transcriptome analysis by RNA sequencing of first trimester plasma RNA, we tested whether the identification of pregnancies at risk of developing pre-eclampsia with or without preterm birth or growth restriction is possible between weeks 9-14, prior to the appearance of clinical symptoms. We implemented a metaheuristic approach in the self-learning SVM algorithm for differential gene expression analysis of normal pregnancies (n = 108), affected pregnancies (n = 34) and non-pregnant controls (n = 19). Presymptomatic candidate markers for affected pregnancies were validated by RT-qPCR in first trimester samples (n = 34) from an independent cohort. PRKG1 was significantly downregulated in a subset of pregnancies with birth weights below the 10thpercentile as shared symptom. The NRIP1/ZEB2 ratio was found to be upregulated in pregnancies with pre-eclampsia or trisomy 21. Complementary quantitative analysis of both the linear and circular forms of NRIP1 permitted discrimination between pre-eclampsia and trisomy 21. Pre-eclamptic pregnancies showed an increase in linear NRIP1 compared to circular NRIP1, while trisomy 21 pregnancies did not.
2.
Ferroportin mRNA is down-regulated in granulosa and cervical cells from infertile women.
Moreno-Navarrete, JM, López-Navarro, E, Candenas, L, Pinto, F, Ortega, FJ, Sabater-Masdeu, M, Fernández-Sánchez, M, Blasco, V, Romero-Ruiz, A, Fontán, M, et al
Fertility and sterility. 2017;(1):236-242
Abstract
OBJECTIVE To explore the relationship between iron and infertility by investigating iron-related gene expression in granulosa and uterine cervical cells. DESIGN Case-control study. SETTING Two tertiary hospitals. PATIENT(S): Two independent cohorts of fertile (n = 18 and n = 17) and infertile (n = 31 and n = 35) women. INTERVENTION(S): In vitro fertilization. MAIN OUTCOME MEASURE(S): Gene expression levels of ferritin light chain (FTL), ferritin heavy chain (FTH), transferrin receptor (TFRC), and ferroportin (SLC40A1) mRNA were analyzed in granulosa and cervical cells. RESULT(S): In the first cohort, fertile and infertile women were similar in body mass index. Ferroportin mRNA levels were decreased in granulosa cells from infertile women in parallel with increased serum hepcidin levels. A positive association between ferroportin and TFRC mRNA, a gene associated with intracellular iron deficiency, was observed only in granulosa cells from fertile women. The major findings were replicated in a second independent cohort. CONCLUSION(S): Ferroportin mRNAs and circulating hepcidin identify a subset of infertile women and may constitute a target for therapy.
3.
Renal systems biology of patients with systemic inflammatory response syndrome.
Tsalik, EL, Willig, LK, Rice, BJ, van Velkinburgh, JC, Mohney, RP, McDunn, JE, Dinwiddie, DL, Miller, NA, Mayer, ES, Glickman, SW, et al
Kidney international. 2015;(4):804-14
Abstract
A systems biology approach was used to comprehensively examine the impact of renal disease and hemodialysis (HD) on patient response during critical illness. To achieve this, we examined the metabolome, proteome, and transcriptome of 150 patients with critical illness, stratified by renal function. Quantification of plasma metabolites indicated greater change as renal function declined, with the greatest derangements in patients receiving chronic HD. Specifically, 6 uremic retention molecules, 17 other protein catabolites, 7 modified nucleosides, and 7 pentose phosphate sugars increased as renal function declined, consistent with decreased excretion or increased catabolism of amino acids and ribonucleotides. Similarly, the proteome showed increased levels of low-molecular-weight proteins and acute-phase reactants. The transcriptome revealed a broad-based decrease in mRNA levels among patients on HD. Systems integration revealed an unrecognized association between plasma RNASE1 and several RNA catabolites and modified nucleosides. Further, allantoin, N1-methyl-4-pyridone-3-carboxamide, and N-acetylaspartate were inversely correlated with the majority of significantly downregulated genes. Thus, renal function broadly affected the plasma metabolome, proteome, and peripheral blood transcriptome during critical illness; changes were not effectively mitigated by hemodialysis. These studies allude to several novel mechanisms whereby renal dysfunction contributes to critical illness.