RBMS3, a gene encoding a glycine-rich RNA-binding protein, belongs to the family of c-Myc gene single-strand binding proteins (MSSP). Recently, several reports have provided evidence that RBMS3 was deregulated in a diverse range of solid tumors and played a critical role in tumor progression. However, it remains unclear whether RBMS3 inhibits the progression of human breast cancer. Thus, the aim of this study was to investigate the role of RBMS3 in breast cancer and explore the underlying mechanism in breast cancer progression. Our results showed, for the first time, that the expression of RBMS3 at both the mRNA and protein levels was significantly downregulated in human breast cancer tissues and cell lines. In addition, RBMS3 overexpression dramatically suppressed the proliferation, migration, and invasion of breast cancer cells in vitro and attenuated tumor growth in vivo. Furthermore, we observed that RBMS3 greatly inhibited the protein expression of β-catenin, cyclin D1, and c-Myc in breast cancer cells. In summary, we have shown that RBMS3 inhibited the proliferation and tumorigenesis of breast cancer cells, at least in part, through inactivation of the Wnt/β-catenin signaling pathway. Thus, RBMS3 may be a potential treatment target for breast cancer.

Alisertib, a potent and selective Aurora kinase A inhibitor, has been demonstrated to exert potent anti-cancer effects in pre-clinical and clinical studies. However, mechanisms of action of alisertib, including the molecular pathways involved in alisertib-induced apoptosis and autophagy of leukemic cells, have remained elusive. The aim of the present study was to investigate the effects of alisertib on cell growth, apoptosis and autophagy and to delineate the possible molecular mechanisms in leukemic cells. Acid phosphatase, MTT and Annexin V/propidium iodide staining assays as well as immunostaining for light chain 3B showed that treatment of the REH leukemia cell line with alisertib exerted potent growth inhibitory effects, and induced apoptosis and autophagy in a dose‑dependent manner. Western blot analysis indicated that these effects may be attributed to the suppression of the activity of the Akt/mammalian target of rapamycin/5'-AMP-dependent kinase/p38 mitogen-activated protein kinase signaling pathways in REH cells. The present study confirmed that alisertib may represent a promising autophagy-inducing drug for the treatment of leukemia and shed light on its molecular mechanism of action.

Background Sepsis is a syndrome of physiological, pathological and biochemical abnormalities caused by infection. Although the mortality rate is lower than before, many survivors have persistent infection, which means sepsis calls for new treatment. After infection, inflammatory mediators were largely released into the blood, leading to multiple organ dysfunction. Therefore, anti-infection and anti-inflammation are critical issues in sepsis management. Results Here, we successfully constructed a novel nanometer drug loading system for sepsis management, FZ/MER-AgMOF@Bm. The nanoparticles were modified with LPS-treated bone marrow mesenchymal stem cell (BMSC) membrane, and silver metal organic framework (AgMOF) was used as the nanocore for loading FPS-ZM1 and meropenem which was delivery to the infectious microenvironments (IMEs) to exert dual anti-inflammatory and antibacterial effects. FZ/MER-AgMOF@Bm effectively alleviated excessive inflammatory response and eliminated bacteria. FZ/MER-AgMOF@Bm also played an anti-inflammatory role by promoting the polarization of macrophages to M2. When sepsis induced by cecal ligation and puncture (CLP) challenged mice was treated, FZ/MER-AgMOF@Bm could not only reduce the levels of pro-inflammatory factors and lung injury, but also help to improve hypothermia caused by septic shock and prolong survival time. Conclusions Together, the nanoparticles played a role in combined anti-inflammatory and antimicrobial properties, alleviating cytokine storm and protecting vital organ functions, could be a potential new strategy for sepsis management.

Background. Hepatocellular carcinoma (HCC) is a kind of primary liver cancer that accounts for more than 90% of primary hepatocellular carcinomas. Hyperuricemia is closely related to the development, recurrence, metastasis, and prognosis of cancer. Previous studies have proved that the serum uric acid level can increase the incidence rate and mortality of malignant tumors. However, the specific pathogenesis remains unstudied. Methods. RT-qPCR analysis showed that the mRNA expression of PDZK1 and ABCG2 increased significantly after HCC cells were exposed to different concentrations of soluble uric acid (2.5, 5, 10, 20 mg/dl) for 24 hours. Then, in HCC shRNAs, PDZK1, or over expression PDZK1 were used. CCK8, wound healing, and Transwell assay showed that PDZK1 regulates cell proliferation, invasion, and migration. Flow cytometry results revealed that PDZK1 affects cell apoptosis. Western blot results show that PDZK1 affects the STAT3/C-myc pathway. Then, in vivo tumorigenesis, allopurinol maybe an effective drug to advance: the prognosis of HCC. Results. In our study, RT-qPCR analysis showed that the mRNA expression of PDZK1 and ABCG2 increased significantly after different concentrations of soluble uric acid in HCC. Then, PDZK1 affects the proliferation, migration, and apoptosis of HCC through the STAT3/C-myc pathway. Conclusions. Hyperuricemia response affects the expression of PDZK1; PDZK1 affects the proliferation, migration, and apoptosis through the STAT3/C-myc pathway in hepatocellular carcinoma. It is suggested that PDZK1 maybe closely related to the occurrence, development, and prognosis of HCC and allopurinol maybe have potential anticancer effects.