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Pre-eclampsia (PE), a pregnancy complication, is a leading cause of maternal and fetal morbidity and mortality. Although its exact etiology and pathogenesis remain elusive, PE results from an interaction of inherited and non‑inherited factors. The clinical symptoms of PE appear post‑mid‑stage of gestation and, at present, there are no early signs/markers for its onset and progression. MicroRNAs function as gene regulators, and are involved in development and pathology. A burgeoning number of studies have highlighted microRNAs as potential biomarkers for minimal invasive assessment. However, it remains a matter of debate as to which microRNA type is involved in PE onset and progression, as well as the clinical utility of testing for these species. In the present review, we have summarized the latest findings on the association of PE with the aberrant expression of placental microRNAs; in particular, those that are detectable in the blood. The current understanding of the mechanisms of microRNA‑target gene interactions that underpin the involvement of microRNAs in the pathogenesis of PE is also discussed.

Sphingosine kinase 1 (SphK1) is an oncogenic lipid kinase that catalyzes the formation of sphingosine-1-phosphate via phosphorylation of sphingosine and known to play a crucial role in angiogenesis, lymphocyte trafficking, signal transduction pathways, and response to apoptotic stimuli. SphK1 has received attention because of its involvement in varying types of cancer and inflammatory diseases such as rheumatoid arthritis, diabetes, renal fibrosis, pulmonary fibrosis, asthma, and neurodegenerative disorders. In the malignancies of breast, lung, uterus, ovary, kidney, and leukemia, overexpression of SphK1 has been reported and thus considered as a potential drug target. In this study, we have performed virtual high-throughput screening of ∼90,000 natural products from the ZINC database to find potential SphK1-inhibitors. Initially, the hits were selected by applying absorption, distribution, metabolism, excretion, and toxicity properties, Lipinski’s rule, and PAINS filters. Further, docking analysis was performed to estimate the binding affinities and specificity to find safe and effective preclinical leads against SphK1. Two compounds, ZINC05434006 and ZINC04260971, bearing appreciable binding affinity and SphK1 selectivity were selected for 100 ns molecular dynamics (MD) simulations under explicit water conditions. The all-atom MD simulation results suggested that the ZINC05434006 and ZINC04260971 binding induces a slight structural change and stabilizes the SphK1 structure. In conclusion, we propose natural compounds, ZINC05434006 and ZINC04260971, as potential inhibitors of SphK1, which may be further exploited as potential leads to develop effective therapeutics against SphK1-associated diseases including cancer after in vitro and in vivo validations.