Beta-2 GPI induced tissue factor and placental apoptosis for the pathophysiology of pregnancy loss in antiphospholipid syndrome

Based on large concurrent studies on human and in vivo results from experimental animals, it is evident that antiphospholipid syndrome (APS) plays a vital role in pregnancy failure in human being. Many underlying pathophysiology including venous thrombosis, thrombocytopenia and placental apoptosis have been demonstrated for the APS-mediated pregnancy loss. On the other hand, Tissue factor (TF) remains considered as a crucial factor for pregnancy morbidity in women with APS globally. Hence, we hypothesize that TF and/or beta-2 glycoprotein – I (β2GPI)-induced TF might play an important role for the increased index of apoptosis in placenta, especially during early stages of fetal development. Further, this could represent as potentially preventable etiology of APS-mediated pregnancy loss in women

Evaluation of anticardiolipin antibodies and antiphosphatidylserine antibodies in women with recurrent abortion

BACKGROUND: Antiphospholipid syndrome (APS) is a major reproductive complication in women, which is characterized by recurrent fetal loss, thrombosis, and thrombocytopenia in association with anticardiolipin antibodies (aCL). AIMS: To analyze the prevalence of aCL and antiphosphatidylserine antibodies (aPS) in relation to pregnancy failures in women with the history of recurrent spontaneous abortion. SETTINGS AND DESIGN: A sequential study of 155 patients, who had three or more recurrent spontaneous abortions, was carried out. METHODS AND MATERIALS: Women with unexplained recurrent pregnancy loss in first trimester were selected for this study. Anticardiolipin antibodies IgG and aPS IgG were detected in the serum by the enzyme linked immunosorbent assay method. STATISTICAL ANALYSIS: Percentage calculation was carried out. Two-tailed t-test was performed to know the significance of aCL and aPS total population. RESULT: The levels of aCL IgG and aPS IgG were detected as 40% (62) and 19% (18), respectively in women with history of recurrent abortion. CONCLUSION: Anticardiolipin antibody is found to be the most important factor for recurrent abortion. In addition, women with negative aCL are having positive for another antiphospholipid antibodies like aPS, which may involve in recurrent abortion

Brain Protective Effect of Resveratrol via Ameliorating Interleukin-1β-Induced MMP-9-Mediated Disruption of ZO-1 Arranged Integrity

In the central nervous system (CNS), the matrix metalloproteinase-9 (MMP-9) is induced by several factors and contributes to CNS disorders, including inflammation and neurodegeneration. Thus, the upregulation of MMP-9 has been considered to be an indicator of inflammation. Interleukin-1β (IL-1β) is an important proinflammatory cytokine which can induce various inflammatory factors, such as MMP-9, in many inflammatory disorders. Several phytochemicals are believed to reduce the risk of several inflammatory disorders, including the CNS diseases. Among them, the resveratrol, a principal phenolic compound of the grape, blueberry, and mulberry peels and Cassia plants, has been shown to possess several medicinal properties, including antioxidative, anti-inflammatory, and antitumor function. Herein, we used mouse-brain microvascular endothelial cells (bMECs) to demonstrate the signaling mechanisms of IL-1β-induced MMP-9 expression via zymographic, RT-PCR, Western blot, reactive oxygen species (ROS) detection, immunofluorescence stain, and promoter reporter analyses. Then we evaluated the effects of resveratrol on IL-1β-induced MMP-9 expression in bMECs and its mechanism of action. We first demonstrated that IL-1β induced MMP-9 expression in bMECs. Subsequently, IL-1β induced MMP-9 expression via ROS-mediated c-Src-dependent transactivation of EGFR, and then activation of the ERK1/2, p38 MAPK, JNK1/2, and NF-κB signaling pathway. Finally, we determined that IL-1β-induced upregulation of MMP-9 may cause the disruption of the arranged integrity of zonula occludens-1 (ZO-1), but this could be inhibited by resveratrol. These data indicated that resveratrol may have antioxidative and brain-protective activities by reducing these related pathways of ROS-mediated MMP-9 expression and tight junction disruption in brain microvascular endothelial cells