Purpose: Cancer stem cells (CSCs) play an important role in various stages of cancer development and therapy refractoriness. 8-Hydroxydaidzein (8-OHD) has revealed anti-cancer activity in different tumors. Accordingly, we aimed to assess the effects of 8-OHD on the suppression of breast cancer stem-like cells (BCSCs). Methods: The anti-proliferative and pro-apoptotic properties of 8-OHD were examined by MTS assay and flowcytometry. The expression levels of stemness markers and JAK2/STAT proteins were measured by quantitative real time-PCR (qRT-PCR) and western blotting, respectively. Results: 8-OHD significantly decreased three out of six stemness markers and remarkably reduced viability and induced apoptosis of spheroidal and parental cells compared to controls. Further experiments using CD95L, as a death ligand, and ZB4 antibody, as an extrinsic apoptotic pathway blocker, showed that 8-OHD induced apoptosis through the intrinsic pathway, proposing a mechanism by which 8-OHD triggers apoptosis. Results of western blot analysis also revealed a marked decline in the phosphorylation of JAK2 and STAT proteins. Conclusion: Our study, for the first time, elucidated an anti-BCSC activity for 8-OHD via decreasing stemness markers, inducing toxicity and stimulating apoptosis in these cells and parental cells. Our results also suggested a novel mechanism by which 8-OHD induces apoptosis in BCSCs.

Liver fibrosis is a disorder in which inflammatory reactions play an important role, and central to the progression and pathogenesis of this disease are the immunespecific cells known as macrophages. Macrophage types are distinguished from each other by the expression of a series of surface markers. STAT6 and Arg1 play an important role in the polarization of macrophages, so these two factors are downstream of interleukin 4 (IL-4) and IL-13 cytokines and cause to differentiate M2. Therefore, this study aimed to compare the independent effects of imatinib and mesenchymal cell treatment on the polarization of macrophages in rat models of liver fibrosis. The liver fibrosis was induced by the injection of CCL4 for 6 weeks in Sprague-Dawley rats. Then, rats were divided into four different groups, and the effects of imatinib and mesenchymal cells on the expression of Arg1, Ly6c, and STAT6 were evaluated. Histopathology experiments considered the amelioration effect of treatments. Our results showed that Arg1 expression was significantly increased in the groups treated with mesenchymal cells and imatinib compared to the control group. On the other hand, expression of STAT6 was significantly increased in the imatinib-treated mice compared to mesenchymal and control groups. Moreover, the expression of LY6C significantly decreased in imatinib and mesenchymal treated groups compared to the control group. Therefore, our data showed that mesenchymal stem cells and imatinib significantly modulate the fibrotic process in rat models of fibrosis, probably by polarizing macrophages towards an anti-inflammatory profile and increasing the frequency of these cells in liver tissue.

Background: Preeclampsia (PE) is a disease characterized by abnormalities in the placenta and endothelial cells. The pathogenesis is not fully understood; however, aspirin prescription can be effective to treat the disease and prevent fetal developmental disorders. Methods: This study was performed as a clinical trial in Shahid Akbrabadi Hospital in Tehran city. Eighty patients participated in two groups (n = 40). The first group of patients received the dose of 80 mg, and the second group received the dose of 160 mg aspirin. Then, the fetal-maternal and treatment process complications were examined in the patients. Results: The results showed that the incidence of fetal-maternal complications, including intrauterine growth restriction (IUGR) and intrauterine fetal death (IUFD) was lower in patients treated with 160 mg aspirin than in the other group, but this difference was not statistically significant (P-value > 0.05). Aspirin complications such as bleeding were more in the second group than in the first one (P-value < 0.05). Conclusions: Although the increasing dose of aspirin reduces fetal-maternal complications in PE patients, the problems such as aspirin-induced bleeding should be considered.