Atherosclerosis is a chronic inflammatory disease; unstable atherosclerotic plaque rupture, vascular stenosis, or occlusion caused by platelet aggregation and thrombosis lead to acute cardiovascular disease. Atherosclerosis-related inflammation is mediated by proinflammatory cytokines, inflammatory signaling pathways, bioactive lipids, and adhesion molecules. This review discusses the effects of inflammation and the systemic inflammatory signaling pathway on atherosclerosis, the role of related signaling pathways in inflammation, the formation of atherosclerosis plaques, and the prospects of treating atherosclerosis by inhibiting inflammation.

Growth factors like insulin-like growth factor 1 (IGF-1) is reported to mediate neurogenesis in the subgranular zone (SGZ) and the subventricular zone (SVZ) of the adult mammalian brain, but its regulatory mechanism remains unclear. We generated transgenic mice overexpressing IGF-1 specifically in neural stem cells (NSCs) and assessed the effect of IGF-1 on neurogenesis in adult mice NSCs. Overexpression of IGF-1 could stimulate the expression of phospho-Akt and phospho-ERK1/2 while inducing proliferation and differentiation of NSCs in the SGZ and SVZ. The MEK/ERK inhibitor U0126 could inhibit ERK1/2 phosphorylation, further inhibiting the proliferation of NSCs in the SGZ and SVZ but had no effect on the phosphorylation of Akt. By contrast, The PI3K/Akt inhibitor LY294002 inhibited phosphorylation of Akt and differentiation of NSCs in the SGZ and SVZ, resulting in no change in the proliferation of NSCs and ERK1/2 phosphorylation. These results demonstrate that IGF-1 upregulates the proliferation of NSCs by triggering MEK/ERK pathway signaling in the adult mice SGZ and SVZ. Meanwhile, IGF-1 also induces differentiation of NSCs via the PI3K/Akt pathway in adult mice. However, we found no evidence of crosstalk between the PI3K/Akt and MEK/ERK pathways in adult mice NSCs. Our work provides new experimental evidence of the involvement of the PI3K/Akt and MEK/ERK pathways in the proliferation and differentiation of the NSCs of adult mice.

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During viral infection, the host cell synthesizes high amounts of viral proteins, which often causes stress to the endoplasmic reticulum (eR). to manage abnormal eR stress, mammalian cells trigger a response called the unfolded protein response (UpR). previous studies have indicated that porcine reproductive and respiratory syndrome virus (pRRSV), an Arterivirus that has been devastating the swine industry worldwide, can induce eR stress and activate UpR, however, the activation pathways and the biological significance requires further investigation. In this study, we demonstrated that, among the three types of UPR pathways, PRRSV infection induced PERK and IRE1 pathways, but not the ATF6 pathway. Furthermore, the induction of UPR promoted PRRSV replication. We also found that pRRSV-induced UpR, particularly the peRK pathway, was involved in the induction of autophagy, a cellular degradation process that can alleviate cell stress. Besides, we also provided insights into the eR stress-mediated apoptosis in response to pRRSV infection. pRRSV infection induced the expression of the transcription factor CHOP, which activated caspase 3 and PARP led to ER stressmediated apoptosis. Using 3-Methyladenine (3-MA) to inhibit autophagy, the increased ER stress and cell apoptosis were observed in the pRRSV infected cell. taken together, our results revealed the associations of eR stress, autophagy, and apoptosis during pRRSV infection, helping us to further understand how pRRSV interacts with host cells. Porcine reproductive and respiratory syndrome (PRRS) caused by PRRS virus (PRRSV), is one of the most economically significant disease in the swine industry 1. PRRSV belongs to the Nidovirales order, Arteriviridae family of positive-sense single-stranded RNA viruses 2. The burden of PRRSV infection on the host cell has been shown to initiate a number of cellular stress responses. Here, we focused on the endoplasmic reticulum (ER) stress during PRRSV infection. The ER is an extensive membranous network that provides a unique environment for the synthesis, maturation, and proper folding of a wide range of proteins. It also plays a critical role in the regulation of calcium concentration and intracellular signal transduction. Endogenous imbalances in cells, such as the accumulation of misfolded or unfolded proteins, can cause a stress to the ER system. To alleviate this stress, the unfolded protein response (UPR) is activated. The UPR eliminates misfolded or unfolded proteins in different ways: (1)

The mechanisms of fetal semi-allograft acceptance by the mother's immune system have been the target of many immunological studies. Early pregnancy factor (EPF) is a molecule present in the serum of pregnant mammals soon after conception that has been reported to have immunomodulatory effects. In the present study, we aimed to determine whether immune cells such as CD4 + CD25 + regulatory T cells (Tregs) are involved in the suppressive mechanism of EPF. Accordingly, CD4 + CD25 -T cells were isolated from spleens of female C57BL/6 mice and stimulated with anti-CD3 antibody, anti-CD28 antibody and IL-2 in the presence or absence of EPF. Flow cytometry was used to analyze the differentiation of CD4 + CD25 -T cells to CD4 + CD25 + Tregs. We thus found a remarkable rise in the Treg ratio in the EPF-treated cells. Higher mRNA and protein levels of fork head box P3 (Foxp3), a marker of the Treg lineage, were also observed in cells treated with EPF. Furthermore, the effect of EPF on Treg immunosuppressive capacity was evaluated. EPF treatment induced the expression of interleukin-10 and transforming growth factor β1 in Tregs. The suppressive capacity of Tregs was further measured by their capability to inhibit T cell receptor-mediated proliferation of CD4 + CD25 -T cells. We thus found that EPF exposure can enhance the immunosuppressive functions of Tregs. Overall, our data suggest that EPF induces the differentiation of Tregs and increases their immunosuppressive activities, which might be an important mechanism to inhibit immune responses during pregnancy.