SummaryThe antiphospholipid syndrome (APS) is an autoimmune disease characterized by the clinical features of recurrent thrombosis in the venous or arterial circulation and fetal losses. Antiphospholipid antibodies (aPL), particularly against the phospholipid binding protein beta-2 glycoprotein I (b2GPI), play an important role in APS pathological mechanisms. aPL can activate intracellular signal transduction in a b2GPI-dependent manner to induce inflammatory responses, and promote hypercoagulable state and recurrent spontaneous abortion when b2GPI is associated with the cell surface receptor. In vivo and in vitro studies show that Annexin A2 (ANXA2) is the high affinity receptor that connects b2GPI to the target cells. However, ANXA2 is not a transmembrane protein and lacks an intracellular signal transduction pathway. Growing evidences suggest that the transmembrane protein toll-like receptor 4 (TLR4) might act as an 'adaptor' for intracellular signal transduction. This review focuses on the role of TLR4 and its signalling pathway in APS pathological mechanisms which will help us better understand the pathological processes of this syndrome.

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The glucocorticoid receptor (GR) is the main effector of the activation of the hypothalamus-pituitary-adrenal (HPA) axis, which is caused by different types of stress that can be divided into two major categories: physical stress and psychological stress. Given the marked presence of GR in the hippocampus, GR-mediated hippocampal injury might be the core event under stress. The aim of this study was to investigate GR expression, hippocampal injury, and behaviors in rats to explore the differences between these types of stressors. Adult male rats were stressed using a classical model (electrical foot shock and a yoked psychologically stressful situation) to induce physical or psychological stress. The GR expression, injury of hippocampal subfields and behavioral abnormalities were dynamic, as demonstrated using immunofluorescence, 3D magnetic resonance imaging (MRI) and open field exploration (OFE), respectively. In addition, housing in a normal environment for 6 weeks was used to verify the recovery ability of rats. First, GR-mediated hippocampal atrophy and behavioral abnormalities were found in the second week under physical stress, but those changes did not appear until the fourth week under psychological stress. Second, the effects of stress were more pronounced after physical stressors than after psychological stressors in the fourth week, but this trend had reversed by the sixth week, especially in the DG (Dentate Gyrus) subfield. Except for the rats that had experienced 6 weeks of psychological stress, all rats showed significant recovery after 6 weeks of housing in a normal environment. The effects of physical stress appeared early but were relatively moderate, whereas the effects of psychological stress appeared late but were more severe. In addition, GR-mediated serious injury in the DG might be the cause of the DG volume loss and behaviors that could not be reversed.

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Objective. The gut microbiota, as the critical mediator of the gut-brain axis, can produce and transport neuroactive substances, thus playing a significant role in the pathogenesis of depression. Although regular physical exercise is an important nondrug antidepressant, its specific effector mechanism is still unclear. Methods. Rats were randomly divided into four different groups (n = 10 for each group) as follows: normal group (G1), depression group (G2), fluoxetine treatment group (G3), and regular exercise treatment group (G4). All rats underwent forced swimming tests, tail suspension tests, open field tests, and elevated plus-maze tests to detect behavioristics. Then, corticosterone levels were detected by ELISA. Additionally, taxonomic analysis of the gut microbiota in all rats was performed after they were exercised regularly for 60 days. Results. Compared with the G1 group, the rats in the G2 group showed significant depression-like behaviors, with increased serum corticosterone levels. The proportions of Bacteroides, Actinomycetes, Proteobacteria, Saccharomyces, and Cyanobacteria in rats of the G2 group were lower than those in the G1 group, while the proportions of Firmicutes, Tenicotte, Deferrobacteria, and Fusobacteria were increased. Furthermore, after regular exercise treatment, the gut microbiota of rats was effectively improved, almost returning to the level of the G1 group, and depressive behavior and corticosterone levels were also restored, which was almost the same as the effect of fluoxetine treatment. Conclusion. Regular physical exercise could alleviate depressive-like behaviors by modulating the species and function of the gut microbiota.