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PC emerges as a good candidate for sPE diagnosis, since it is a simple and habitually done method, with lower cost and greater accessibility in the clinical laboratory. Further studies evaluating sequential PC and platelet indices throughout pregnancy are necessary to clarify the role of platelet parameters in PE development and severity.

Although preeclampsia causes high maternal/fetal morbidity and mortality, the etiology of this multi-system disorder still remains to be elucidated. Herein, we have characterized the cytokine plasma levels in severe preeclamptic women compared to normotensive pregnant and non-pregnant women, aiming to better understand the immunological network and its clinical significance for the pathogenesis and severity of preeclampsia. A total of 219 women were selected. The study population was composed of three groups referred as severe preeclamptic, normotensive pregnant and non-pregnant women. Cytokine plasma levels were determined using commercially available kits, Cytometric Beads Array - CBA to quantify TNF-α, IFN-γ, IL-4, IL-5, IL-10, IL-1β, IL-6, IL-8 and IL-12. Our findings demonstrated that severe preeclamptic state is associated with high levels of pro-inflammatory cytokines IL-8, IL-6, and IFN-γ (P < 0.05 for all) whereas normotensive pregnancy evolves high levels of regulatory cytokine IL-10 (P < 0.05). Moreover, an outstanding pro-inflammatory "cytokine signature" could be observed in severe preeclamptic women display, while an overall regulatory state is the hallmark for normotensive pregnancy. In summary, our data showed that elevated levels of pro-inflammatory cytokines in the maternal circulation with a deviation in the "IL-8 × IL-6" axis towards IFN-γ might drive the cytokine network in preeclamptic women towards an excessive systemic inflammatory state.

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The results taken together indicate the presence of a hypercoagulability state in women with operable hormone receptor-negative breast cancer given the increased levels of D-dimer in this group. Therefore, considering higher levels of D-dimer in patients with a poor outcome, its evaluation may be a promising tool for prognosis in women with operable hormone receptor-negative breast cancer.

The plasminogen (Plg)/plasmin (Pla) system is associated with a variety of biological activities beyond the classical dissolution of fibrin clots, including cell migration, tissue repair, and inflammation. Although the capacity of Plg/Pla to induce cell migration is well defined, the mechanism underlying this process in vivo is elusive. In this study, we show that Pla induces in vitro migration of murine fibroblasts and macrophages (RAW 264.7) dependent on the MEK/ERK pathway and by requiring its proteolytic activity and lysine binding sites. Plasmin injection into the pleural cavity of BALB/c mice induced a time-dependent influx of mononuclear cells that was associated with augmented ERK1/2 and IκB-α phosphorylation and increased levels of CCL2 and IL-6 in pleural exudates. The inhibition of protease activity by using a serine protease inhibitor leupeptin or two structurally different protease-activated receptor-1 antagonists (SCH79797 and RWJ56110) abolished Pla-induced mononuclear recruitment and ERK1/2 and IκB-α phosphorylation. Interestingly, inhibition of the MEK/ERK pathway abolished Pla-induced CCL2 upregulation and mononuclear cell influx. In agreement with a requirement for the CCL2/CCR2 axis to Pla-induced cell migration, the use of a CCR2 antagonist (RS504393) prevented the Plg/Pla-induced recruitment of mononuclear cells to the pleural cavity and migration of macrophages at transwell plates. Therefore, Pla-induced mononuclear cell recruitment in vivo was dependent on protease-activated receptor-1 activation of the MEK/ERK/NF-κB pathway, which led to the release of CCL2 and activation of CCR2.

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Pre-eclampsia (PE) is a multi-system disorder of human pregnancy, characterised by hypertension and proteinuria. Although the pathogenesis of PE is not fully understood, predisposition to endothelial dysfunction is thought to play a crucial part. Despite intensive research there is no reliable test for screening purposes or to inform decision making towards effective treatment for PE. Understanding the link between PE, abnormal haemostatic activation and inflammation may help to elucidate some of the patho-physiology of the disease; primary preventative measures and targeted therapies at an early stage of the disease could then be considered. In the present paper we discuss potential causal links between PE, haemostasis and inflammation. The potential implications of such interaction on the pathogenesis of PE are also addressed.