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Breast cancer has been the most commonly-diagnosed cancer worldwide, and the treatment and prognosis of which are often limited by breast cancer stem cells (BCSCs). Litchi seeds have shown good anti-cancer activity in various cancers including prostate cancer, lung cancer and breast cancer. However, the activity and underlying mechanism of Litchi seeds against BCSCs remain unknown. To investigate the activity and mechanism of total flavonoids of litchi seed (TFLS) against BCSCs in vitro and in vivo. Two orthotopic xenograft mouse models were established using HCC1806 cells pretreated or untreated with TFLS to determine whether TFLS could target BCSCs in vivo. Mammosphere formation and flow cytometry assays were employed to evaluate the effect of TFLS on BCSCs in vitro. The underlying mechanism was investigated using RT-qPCR, Western blot, immunohistochemistry and immunofluorescence experiments. TFLS could significantly inhibit the viability of HCC1806, MCF-7 and HCC1937 cells in vitro and suppress the growth of HCC1806 cells in vivo. TFLS attenuated stem cell-like properties of breast cancer through reducing the percentage of CD44+CD24-/low cells, inhibiting the mammospheres formation and down-regulating the mRNA and protein levels of cancer stem cells related markers (Oct4, Nanog, Sox2) in MCF-7 and HCC1806 cells. Meanwhile, TFLS suppressed the tumor-initiating ability of BCSCs via reducing the percentage of CD44+CD24-/low cells in tumor and lowering tumor incidence rate in orthotopic xenograft mice. In addition, TFLS treatments restricted the expression and nuclear translocation of Notch3, subsequently down-regulated Hes1 and Runx2 expressions. TFLS could suppress the growth of breast cancer and eliminate breast cancer stem cells by inhibiting the Notch3 signaling pathway. [Display omitted] • TFLS inhibit breast cancer in vitro and in vivo. • TFLS attenuate breast cancer stem cells in vitro and restrict their tumorigenic ability in vivo. • TFLS decrease the expression and nuclear translocation of Notch3, subsequently down-regulate Hes1 and Runx2 expressions. [ABSTRACT FROM AUTHOR]

Estrogen plays an essential role in bone formation, and estrogen modulation dysfunction is tightly associated with postmenopausal osteoporosis (PMOP). The underlying mechanisms of estrogen-mediated osteogenic differentiation have not been well defined. In this study, murine bone marrow mesenchymal stem cells were induced to undergo osteogenic differentiation, and gene expression analysis or GPR40 expression manipulation was performed. Bilateral ovariectomized or sham-operated C57BL/6 mice were administered GPR40 agonist (GW9508) for bone mineral density analysis. We identified GPR40, a long chain unsaturated fatty acid receptor, to be regulated by estrogen and involved in osteogenic differentiation both in vivo and in vitro . Mechanistically, the Wnt/β-catenin signaling pathway is essential for GPR40 to promote osteogenic differentiation. Furthermore, in vivo GW9508 administration rescued estrogen-deficient bone loss, indicating the essential role of the GPR40 receptor. To our knowledge, this is the first study that provides evidence for GPR40 as a positive regulator of osteogenesis and Wnt/β-catenin signaling. These results indicate that GPR40 may function as an endogenous promoter of estrogen-induced osteogenic differentiation through Wnt/β-catenin signaling activation. Therefore, as the global population of ages and the prevalence of metabolic-related disorders, especially PMOP, increases, our findings suggest that GPR40 is a key in understanding the link between bone and fat. It may also be a useful target for the treatment of bone complications in the future. [ABSTRACT FROM AUTHOR]

Abstract: The present study examined the protective effect of hyperbaric oxygen preconditioning (HBO-PC) and the role of thioredoxin reductase (TrxR) in a post-traumatic stress disorder (PTSD)-induced rat model by using single prolonged stress (SPS). Rats were randomly divided into Sham, HBO, SPS and HBO+SPS groups. HBO-PC was conducted by exposing rats to 100% oxygen at 2.5atm absolute for 1h each day for 5 consecutive days. SPS was performed 24h after the last HBO-PC conditioning event. At 1h, 6h, 12h, 24h and 72h after SPS, TrxR mRNA expression was analyzed in the hippocampus; Nissl and TUNEL staining were performed at 72h after SPS. The results indicated that HBO-PC was able to significantly preserve viable neurons in the CA1 subfield of hippocampus following SPS exposure, as evidenced by reduced amounts of CA1 neuronal apoptosis. Furthermore, HBO-PC upregulate the expression of TrxR-1 and TrxR-2 mRNA in the hippocampus at 6h and 12h after SPS exposure and ameliorated anxiety-like behavior and cognitive impairments normally induced by SPS. Taken together, these findings suggest that HBO-PC is beneficial for the improvement of anxiety-like behavior and cognitive impairments induced by SPS exposure, and this effect might be associated with inhibition of neuronal apoptosis via upregulation of TrxR in stressed rats. [Copyright &y& Elsevier]