Metabolic reprograming is a hallmark of cancer, and the polyamine metabolic network is dysregulated in many cancers. Ornithine decarboxylase (ODC) is a rate‐limiting enzyme for polyamine synthesis in the polyamine metabolic network. In many cancer cells, ODC is over‐expressed, so this enzyme has been an attracting anti‐cancer drug target. In the catalysis axis (pathway), ODC converts ornithine to putrescine. Meanwhile, ODC’s activity is regulated by protein–protein interactions (PPIs), including the ODC‐OAZ1‐AZIN1 PPI axis and its monomer‐dimer equilibrium. Previous studies showed that when ODC’s activity is inhibited, the PPIs might counteract the inhibition efficiency. Therefore, we proposed that multipurpose inhibitors that can simultaneously inhibit ODC’s activity and perturb the PPIs would be very valuable as drug candidates and molecular tools. To discover multipurpose ODC inhibitors, we established a computational pipeline by combining positive screening and negative screening. We used this pipeline for the forward screening of multipurpose ligands that might inhibit ODC’s activity, block ODC‐OAZ1 interaction and enhance ODC non‐functional dimerization. With a combination of different experimental assays, we identified three multipurpose ODC inhibitors. At last, we showed that one of these inhibitors is a promising drug candidate. This work demonstrated that our computational pipeline is useful for discovering multipurpose ODC inhibitors, and multipurpose inhibitors would be very valuable. Similar with ODC, there are a lot of proteins in human proteome that act as both enzymes and PPI components. Therefore, this work is not only presenting new molecular tools for polyamine study, but also providing potential insights and protocols for discovering multipurpose inhibitors to target more important protein targets.

Background: Neutrophil-lymphocyte ratio (NLR) is one of the markers of systemic inflammation. Recent studies have associated NLR with diagnosis of preeclampsia (PE). However, due to small sample sizes and different research design, the diagnostic value of NLR in PE patients is not well understood. In this study, we evaluate the potential diagnostic value of NLR in PE. Methods: We searched PubMed, Embase, Cochrane Library, the Chinese National Knowledge Infrastructure (CNKI) databases, Wanfang data, VIP database and China Biomedical Literature Database systematically for relevant literatures up to May 20, 2018. All analyses were conducted using Meta-DiSc1.4 and Stata 12.0 software. Sensitivity, specificity and other measures of accuracy of NLR for the diagnosis of PE were pooled. Meta-regression was performed to identify the sources of heterogeneity. Results: This meta-analysis included a total of 7 studies. The pooled sensitivity and specificity were 0.74 (95% CI 0.71–0.76) and 0.64 (95%CI 0.61–0.68), positive likelihood ratio, 2.62 (95%CI1.79–3.84); negative likelihood ratio, 0.34 (95%CI 0.24–0.48); diagnostic odds ratio, 8.44 (95%CI 4–17.78), and area under the curve was 0.82. Meta regression showed that sample size was the main source of heterogeneity. Deeks funnel plot showed that there was no statistical significance for the evaluation of publication bias (P = .16). Conclusion: Current evidence suggests that the diagnostic accuracy of NLR has unsatisfactory specificity but acceptable sensitivity for diagnosis of PE. Further large-scale prospective studies are required to validate the potential applicability of using NLR alone or in combination other markers as PE diagnostic biomarker and explore potential factors that may influence the accuracy of NLR for PE diagnosis.

Objective This study aims to identify the effect of miR-146a-5p on trophoblast cell invasion as well as the mechanism in preeclampsia (PE). Methods Expression levels of miR-146a-5p and Wnt2 in preeclamptic and normal placentae were quantified. Trophoblast cells (HTR-8) were separately transfected with miR-146a-5p mimic, miR-146a-5p inhibitor, pcDNA3.1-Wnt2 or sh-Wnt2, and then the expression levels of miR-146a-5p, Wnt2, and epithelial-mesenchymal transition (EMT)-related proteins (Vimentin, N-cadherin and E-cadherin) were measured. Moreover, the proliferative, migratory and invasive capacities of trophoblast cells were detected, respectively. Dual luciferase reporter assay determined the binding of miR-146a-5p and Wnt2. Results Compared with normal placental tissues, the placentae from PE patients showed higher miR-146a-5p expression and lower Wnt2 expression. Transfection of miR-146a-5p inhibitor or pcDNA3.1-Wnt2 exerted pro-migratory and pro-invasive effects on HTR-8 cells and encouraged EMT in HTR-8 cells; transfection with miR-146a-5p mimic or sh-Wnt2 weakened the proliferative, migratory and invasive capacities as well as reduced EMT process of HTR-8 cells. Moreover, Wnt2 overexpression could partially counteract the suppressive effects of miR-146a-5p overexpression on the progression and EMT of HTR-8 cells. Conclusion miR-146a-5p mediates trophoblast cell proliferation and invasion through regulating Wnt2 expression.